Abstract
Mitogen-Activated Protein Kinase (MAPK) pathway is a signal transduction pathway that functions in a wide range of physiological and pathophysiological cellular events including cell proliferation, differentiation, apoptosis, migration, inflammation, metabolic disorders and diseases. In skeletal muscle, it plays an essential role in muscle fiber specialization, muscle mass maintenance, damage induced muscle regeneration and muscle diseases. This review provides an overview of MAPK pathway and its pathophysiological role in skeletal muscle diseases with a primary focus on muscular dystrophy and atrophy.
Brief introduction of post-translational modifications (PTMs)Creative Proteomics
PTMs are chemical alterations to protein structure, typically catalyzed by exceedingly substrate-specific enzymes, which themselves are under strict control by PTMs. They generate a large diversity of gene products because many types of PTMs are covalently attached to amino-acid residues in each protein. For protein post-translational modification analysis at Creative Proteomics, please visit https://www.creative-proteomics.com/services/protein-post-translational-modification-analysis.htm
Mass spectrometry (MS) is the suitable method for the analysis of protein modifications because it can provide universal information about protein modifications without a priori knowledge and locating the sites of modification.
If you are interested in our services, please visit: https://www.creative-proteomics.com/services/protein-post-translational-modification-analysis.htm
Brief introduction of post-translational modifications (PTMs)Creative Proteomics
PTMs are chemical alterations to protein structure, typically catalyzed by exceedingly substrate-specific enzymes, which themselves are under strict control by PTMs. They generate a large diversity of gene products because many types of PTMs are covalently attached to amino-acid residues in each protein. For protein post-translational modification analysis at Creative Proteomics, please visit https://www.creative-proteomics.com/services/protein-post-translational-modification-analysis.htm
Mass spectrometry (MS) is the suitable method for the analysis of protein modifications because it can provide universal information about protein modifications without a priori knowledge and locating the sites of modification.
If you are interested in our services, please visit: https://www.creative-proteomics.com/services/protein-post-translational-modification-analysis.htm
Introduction
Protein modifications
Folding
Chaperon mediated
Enzymatic
Cleavage
Addition of functional groups
Chemical groups
Hydrophobic groups
Proteolysis
Conclusion
Reference
Investigating Chemical Chaperones that can improve the stability of Lysozymes...oyepata
Investigating Chemical Chaperones that can improve the stability of Lysozymes
under high thermal temperature.
Sabastine Aliyu Zubairu1, Joseph Oyepata Simeon2, Isaac Ralph Elon1, Mahdi
Mohammed1, Sunday Blessing
Mitochondria are double membranous organelle, the inner membrane is more larger than the outer one. For this reason the inner membrane of the mitochondria folds inside forming a special figure called creasteae. The inner mitochondrial membrane (IMM) contains the subunits for oxidative phosphorylation (OXPHOS). And this inner mitochondrial membrane coverd by a second membrane called the outer mitochondrial membrane (OMM). We called mitochondria as a power house of cell not only they generates ATP via oxidative phosphorylation they also take part in various biochemical pathways such as- pyrimidine and purine biosynthesis, heme biosynthesis, the regulation of N2 balance in urea cycle, gluconeogenesis, keton body production and fatty acid degradation and elongation. They also take part in cell signalling via regulating the protein-protein interaction or by regulating the cellular concentration of calcium ion(Ca2+) and reactive oxygen species(ROS).
During various biological diseasesmitochondrial morphology altered, as in the case when there is lack of nutrient in our body mitochondria combine together to share their nutrient and alo their DNA and ETC components to maintain their OXPHOS. But in case of high energy demand of a part of body mitochondria undergo division or called fission because they move rapidly than lager one (Zhao et al., 2013). Fission also occur in mitotic cell to share equal amount of mitochondria to the daughter cells. Many questions arise in mitochondrial dinamics but here I am going to answer a most doubtful question- Is mitochondrial dynamics play any role in tumorigenic process? Is any oncogenic signalling play crucial role in morphological alteration of mitochondria?
Introduction
Protein modifications
Folding
Chaperon mediated
Enzymatic
Cleavage
Addition of functional groups
Chemical groups
Hydrophobic groups
Proteolysis
Conclusion
Reference
Investigating Chemical Chaperones that can improve the stability of Lysozymes...oyepata
Investigating Chemical Chaperones that can improve the stability of Lysozymes
under high thermal temperature.
Sabastine Aliyu Zubairu1, Joseph Oyepata Simeon2, Isaac Ralph Elon1, Mahdi
Mohammed1, Sunday Blessing
Mitochondria are double membranous organelle, the inner membrane is more larger than the outer one. For this reason the inner membrane of the mitochondria folds inside forming a special figure called creasteae. The inner mitochondrial membrane (IMM) contains the subunits for oxidative phosphorylation (OXPHOS). And this inner mitochondrial membrane coverd by a second membrane called the outer mitochondrial membrane (OMM). We called mitochondria as a power house of cell not only they generates ATP via oxidative phosphorylation they also take part in various biochemical pathways such as- pyrimidine and purine biosynthesis, heme biosynthesis, the regulation of N2 balance in urea cycle, gluconeogenesis, keton body production and fatty acid degradation and elongation. They also take part in cell signalling via regulating the protein-protein interaction or by regulating the cellular concentration of calcium ion(Ca2+) and reactive oxygen species(ROS).
During various biological diseasesmitochondrial morphology altered, as in the case when there is lack of nutrient in our body mitochondria combine together to share their nutrient and alo their DNA and ETC components to maintain their OXPHOS. But in case of high energy demand of a part of body mitochondria undergo division or called fission because they move rapidly than lager one (Zhao et al., 2013). Fission also occur in mitotic cell to share equal amount of mitochondria to the daughter cells. Many questions arise in mitochondrial dinamics but here I am going to answer a most doubtful question- Is mitochondrial dynamics play any role in tumorigenic process? Is any oncogenic signalling play crucial role in morphological alteration of mitochondria?
Metabolic investigation of segmental overgrowth: new insights in pathogenic m...BiologInc
[Biolog Webinar] Dr. Luigi Boccuto's presentation of his investigation of the pathogenic mechanisms of segmental overgrowth caused by mosaic mutations in the genes of the PI3K-AKT pathway. He will describe how Biolog Phenotype MicroArray™ Technology is used to identify new treatment targets and test compounds with potential therapeutic effects.
Corticosteroid induced disorders – An overviewpharmaindexing
Glucocorticoids are important in the treatment of many inflammatory, allergic, immunologic, and malignant disorders, and the toxicity of glucocorticoids is one of the commonest causes of iatrogenic illness associated with chronic inflammatory disease.Glucocorticoid-induced muscle atrophy is characterized by fast-twitch or type II muscle fiber atrophy. Corticosteroid (CS) therapy is widely used in the treatment of rheumatic diseases.Osteoporosis remains one of its major complications.Steroid induced glaucoma is a form of open angle glaucoma occurring as an adverse effect of corticosteroid therapy. Glucocorticoids induce hepatic and extrahepatic insulin resistance.Glucocorticoid treatment impairs both glucose transport in fat and muscle cells. Corticosteroid-induced psychosis represents a spectrum of psychological changes that can occur at any time during treatment. Cushing’s syndrome describes the signs and symptoms associated with prolonged exposure to inappropriately high levels of the hormone cortisol. Physicians must be aware of these adverse effects and be equipped to manage them.
Journal of Nutrition and Health Sciences is an open access journal that publishes peer reviewed research articles and short communications in all aspects of nutrition. This Journal encompasses the full spectrum of nutritional science including nutritional requirements, public health nutrition, epidemiology, dietary surveys, body composition, energetics, appetite, obesity, ageing and metabolic studies.
Journal of Proteomics & Geneomics (JPG) is an instructional journal providing a chance to researchers and scientists to explore the advanced and latest research developments within the field of Proteomics and Geneomics. Journal of Proteomics & Geneomics publishes the best quality scientific articles amalgamating broad vary of fields together with the fields associated with Proteomics & Geneomics.
Journal of Obesity and Overweight (JOO) is a peer reviewed open access journal. It is dedicated to increase knowledge, fostering research, and promoting better treatment for people with obesity. It includes subjects like nutrition medicine, clinical nutrition medicine, genetics and nutrition, biophysics and lipid metabolism, etc. It aims to publish advanced research works related to public health and medical developments.
Journal of Computational Systems Biology (JCSB) is an open access online journal which aims to publish peer reviewed research articles and short communications in all aspects of computational biology and bioinformatics. JCSB comprehend the broad spectrum of computational bioscience including biological databases and bioalgorithms.
Journal of Biometrics and Its Applications (JBIA) is peer reviewed open access journal which addresses the fundamental areas in computer science that deal with biological measurements. It covers both the theoretical and practical aspects of human identification and verification. Biometrics based authentication, an integral component of identity science, is now being utilized in several applications playing a central role in personal, national and global security. Biometric refers to the field of development of statistical and mathematical methods applicable to data analysis problems in the biological sciences.
Journal of Gynecology Research (JGR) publishes original articles and research studies on, scientific advances, new medical and surgical techniques, obstetric management, and clinical evaluation of drugs and instruments and all aspects of gynecology including gynecological endoscopy, infertility, oncology contraception, urogynecology, fertility, and clinical practice and ultrasonography. It aims to publish the highest quality medical research in women's health, worldwide.
CLINICAL AND EXPERIMENTAL RESEARCH IN CARDIOLOGYAnnex Publishers
Journal of Clinical and Experimental Research in Cardiology (JCERC) is an international open access, scholarly peer-reviewed journal publishing high quality articles in all areas of cardiology related fields, especially current research, new concepts, novel methods, new therapeutic agents, and approaches for early detection and prevention of cardiac disorders and reporting new methods on basic and advanced clinical aspects of cardiology research.
Journal of Genetic Mutations and Disorders (JGMD) is an open access, peer reviewed journal which provides advanced researches including Genetics of Infectious Diseases, Genealogical Tracing, Stem Cell Research, Gene mapping with three-point crosses, Genetic linkage and genetic maps. JGMD publishes original research, review articles in all aspects of genetic mutations and disorders
CLINICAL AND EXPERIMENTAL RESEARCH IN CARDIOLOGYAnnex Publishers
Journal of Clinical and Experimental Research in Cardiology (JCERC) is an international open access, scholarly peer-reviewed journal publishing high quality articles in all areas of cardiology related fields, especially current research, new concepts, novel methods, new therapeutic agents, and approaches for early detection and prevention of cardiac disorders and reporting new methods on basic and advanced clinical aspects of cardiology research.
Journal of Bioequivalence Studies (JBS) is an open access, peer reviewed journal that publishes the most relevant and reliable researches with respect to the subject of Bioequivalence studies which includes pharmacokinetic and pharmcodynamic properties of a drug. JBS publishes original articles, review articles, case reports, short communications, etc.
Journal of Forensic Science & Criminology (JFSC) is an open access, significant and reliable source of contemporary knowledge on advancements in the field of forensic science. JFSC publishes peer reviewed research articles, critical reviews and short communications focused on forensic science and criminology. JFSC encompasses the full spectrum of forensic science including forensic biology, forensic chemistry, cyber forensics and crime scene investigation
Annex Publishers, as an Open Access publication model allows the dissemination of research articles to the worldwide community. We offer you the advantage of interaction with the most effective minds from the scientific community. All articles printed under open access will be accessed by anyone.
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JOURNAL OF VETERINARY SCIENCE & ANIMAL HUSBANDRYAnnex Publishers
Journal of Veterinary Science and Animal Husbandry (JVSAH) is a scientific journal which has topics associated with fundamental and aspects of veterinary science and animal husbandry. JVSAH has a special feature of publishing special issues in experimental clinical research, veterinary medicine and current research. At Annex Publishers, we tend to publish quality articles and try our best to provide the most effective analysis journal to the scientific community.
Anti arthritic-efficacy-and-safety-of-crominex-3+(trivalent-chromium-phyllant...Annex Publishers
Abstract
The present investigation was undertaken to evaluate the therapeutic efficacy and safety of Crominex® 3+ (a complex of trivalent chromium, Phyllanthus emblica (Amla) extract and purified Shilajit) in moderately arthritic dogs. Eleven client-owned moderately arthritic dogs in a randomized double-blinded study received placebo or Crominex® 3+ twice daily for a period of 150 days. On a monthly basis, each dog was evaluated for arthritis associated pain (overall pain, pain upon limb manipulation and pain after physical exertion) and a full physical exam (body weight, body temperature and heart rate). At the same time intervals, dogs serum samples were examined for biomarkers of kidney (BUN and creatinine), liver (bilirubin, ALT and AST) and heart and skeletal muscle (CK) functions. Findings of this investigation revealed that dogs receiving Crominex® 3+ (1000 μg chromium, 15 mg Amla extract and 15 mg purified Shilajit per day in two divided doses) exhibited a significant (P< 0.05) reduction in arthritic pain noted as early as after 90 days with a maximum reduction after 150 days of treatment. Pain level remained the same or slightly increased in the dogs receiving placebo. No significant change occurred in physical parameters or serum biomarkers in dogs on placebo or Crominex® 3+, which suggested that Crominex® 3+ was well tolerated by arthritic dogs. In conclusion, Crominex® 3+ significantly (P< 0.05) ameliorated arthritic pain and improved quality of life without causing any untoward effects in moderately arthritic dogs.
Abstract
The objectives of this retrospective study were 1. To determine the effect of three surgical techniques (right flank omentopexy, right flank omentoabomasopexy, and left flank abomasopexy), and 2. To determine the effect of concurrent disease on return to normal milk production. Return to normal milk production occurred in 86.3% of cows diagnosed with LDA. Results suggested that cattle diagnosed with LDA corrected via right flank omentopexy or left flank abomasopexy were significantly more likely to return to normal milk production as compared to those corrected via right flank omentoabomasopexy (p< 0.02). No significant difference in return to normal milk production was noted between surgical techniques for correction of RDA (p=1.000) and right abomasal volvulus (p=0.596). Concurrent disease diagnoses did not affect return to milk production. Reported complications were infrequent (n=11).
List of abbreviations: LDA- Left displaced abomasum; RDA- Right displaced abomasum; RAV- Right abomasal volvulus; RAOV- Right abomasal-omasal volvulus; RFO- Right flank omentopexy; RFOA- Right flank omentoabomasopexy; LFA- Left flank abomasopexy; DA – Displaced Abomasum
Abstract
Three surgical case reports are presented to demonstrate the clinical efficacy of using an improved aqueous solution of chlorine dioxide complex (160 ppm) as a topical antiseptic in the post operative management of serious wounds in dogs. In vitro studies are included to demonstrate the antiseptic properties of this new chlorine dioxide complex.
Keywords: Chlorine dioxide; Antiseptic; Antimicrobial; Wound management
Abbreviations: ClO2-Chlorine dioxide; Cl2-Chlorine; PPM-Parts Per Million; SPP-Species; TEM-Transmission Electron Micrograph
Abstract
Salmonella is a causative agent for a wide variety of pathological diseases in humans, cattle, poultry and other farm animals and hence Salmonella infections are a major cause of concern to humans, veterinary animals and to food industry. With characterization of over 2500 Salmonella serovars, the pathogen nearly infects all vertebrates but the severity of infection varies from one serovar to another depending upon their host specificity. Some Salmonella serovars are restricted to one or few hosts while others have a broad host spectrum. Thus the understanding of the mechanisms involving host preference by one serovar over another is very important. As our knowledge about host adaptability will then be instrumental in designing better vaccines. Furthermore, methods involving identification of genetic markers for host specificity will prove to be instrumental in determining virulence factors for other pathogenic bacteria that cause systemic infections.
Keywords: Host adaption; Evolution; Salmonella serovar; Horizontal gene transfer
Anti inflammatory-and-anti-arthritic-efficacy-and-safety-of-purified-shilajit...Annex Publishers
Abstract
The objective of this investigation was to evaluate the efficacy and safety of purified Shilajit in moderately arthritic dogs. Ten client-owned dogs in a randomized double-blinded study received either a placebo or Shilajit (500 mg) twice daily for a period of five months. Dogs were evaluated each month for physical condition (body weight, body temperature, heart rate, and respiration rate) and pain associated with arthritis (overall pain, pain from limb manipulation, and pain after physical exertion). Serum samples collected from these dogs were examined each month for biomarkers of liver (bilirubin, ALT, and AST), kidney (BUN and creatinine) heart and muscle (creatine kinase) functions. The findings of this study revealed that dogs receiving Shilajit (Group-II) showed a significant (P< 0.05) reduction in pain from limb manipulation by day 60, and overall pain and pain after physical exertion by day 120. Maximum pain reduction, using all three criteria, was observed on day 150. Pain level remained significantly unchanged in dogs receiving the placebo. Dogs in either group showed no significant change (P>0.05) in physical parameters or serum markers, suggesting that Shilajit was well tolerated by moderately arthritic dogs. It was concluded that Shilajit significantly (P< 0.05) reduced pain in osteoarthritic dogs and markedly improved their daily life without any side effects.
Keywords: Purified Shilajit; Osteoarthritis in canine; Shilajit safety; Anti-arthritic nutraceutical
The updated-international-veterinary-anatomical-and-embryological-nomenclaturesAnnex Publishers
The international nomenclature of the anatomical, histological and embryological terms is known as Nomina Anatomica Veterinaria (N.A.V.), Nomina Histologica Veterinaria (N.H.V.) and Nomina Embryologica Veterinaria (N.E.V.).
This is the tripod of terms for the morphological sciences in our profession, a dictionary of terms used by all specialists in the basic and in the clinical sciences.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
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Volume 1 | Issue 1 Abstract
Mitogen-Activated Protein Kinase (MAPK) pathway is a signal transduction pathway that functions in a wide range of physiological and pathophysiological cellular events including cell proliferation, differentiation, apoptosis, migration, inflammation, metabolic disorders and diseases. In skeletal muscle, it plays an essential role in muscle fiber specialization, muscle mass maintenance, damage induced muscle regeneration and muscle diseases. This review provides an overview of MAPK pathway and its pathophysiological role in skeletal muscle diseases with a primary focus on muscular dystrophy and atrophy.
MAPK pathway consists of at least 4 subfamilies that include extracellular signal-regulated kinase 1 and 2 (ERK 1/2), p38α/β/γ/δ MAPK, c-Jun NH2-terminal kinases 1, 2, and 3 (JNK 1/2/3), and ERK5 [1-4]. MAPKs are a family of protein phosphorylating enzymes [5] that regulate diverse aspects of cellular responses in physiology, immunology, neurobiology, and energy metabolism [6]. Cellular activities regulated by MAPKs include proliferation, differentiation, apoptosis, motility [7,8], stress responses, inflammation, and innate immunity [9-11]. MAPK functions through transcriptional activation and posttranslational modification on the downstream substrates. Specifically, MAPKs are involved in the production of antimicrobial factors, cytokines, chemokines, and other inflammatory mediatory factors [12]. In the central nervous system, MAPKs are required for proper neuronal axonal development [13]. MAPKs also play a critical part in energy metabolism through modulating lipid metabolism [14-16] and skeletal muscle growth and fiber type [6]. Given the fact that MAPKs play such a fundamental and integral role in a broad range of biological processes, interference of this pathway and their downstream effector proteins may have detrimental consequences leading to either metabolic disorder or diseases. This review mainly focuses on the functional role of MAPK pathway in skeletal muscle diseases. MAPK Pathway
MAPK Pathway in Skeletal Muscle Diseases
Hannah W.S. Geisler, Hao Shi* and David E. Gerrard
Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, USA
*Corresponding author: Hao Shi, Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, 304 Litton-Reaves Hall, Blacksburg, VA 24061, USA, Fax: (540) 231-3010, Tel: (540) 231-9663, E-mail: haoshi@vt.edu
Citation: Hannah W.S. Geisler, Hao Shi, David E. Gerrard (2013) MAP Kinase Pathway in Skeletal Muscle Diseases. J Vet Sci Anim Husb 1(1): e104. doi: 10.15744/2348-9790.1.e104
Received Date: July 08, 2013 Accepted Date: July 29, 2013 Published Date: August 01, 2013
Editorial
Open Access
MAPKs phosphorylate serine and threonine residues on their substrates [8] which may include protein kinases, phospholipids, transcription factors and even cytoskeletal proteins [17]. MAPKs are activated through a three-tiered phosphorylation relay that transmits signals from the cell surface into biochemical responses: MAPKs are phosphorylated and thus activated by upstream Mitogen-Activated Protein Kinase Kinases (MKKs) which are phosphorylated and activated by their upstream MKK kinases (MKKKs) [18,19]. Given the fact that each tier of phosphorylation consists of multiple kinases, one may question how an extracellular signal is decoded and transduced into a specific cellular response in a temporal and spatial manner. The complexity of regulation of the MAPKs provides a platform on which diverse signals converge and are precisely deciphered to generate a specific signal that fine-tunes the signaling network within a cell. On the other hand, an activated MAPK signal has to be curtailed in a timely manner so that cell will not overreact to a stimulus so to maintain metabolic homeostasis. One mechanism involves the dephosphorylation and thus inactivation of MAPKs by the MAPK phosphatases (MKPs) [5]. MKPs, also known as dual-specificity protein phosphatases (DUSPs), are a group of 10 catalytically active protein tyrosine phosphatases [9,20,21]. MKPs inactivate MAPKs through dephosphorylation of MAPKs on regulatory threonine and tyrosine residues. Though the substrates of the MKPs are to some extent overlapping, MKPs achieve their substrate specificity through binding affinity and sub-cellular localization [22]. MAPKs and Muscular Dystrophy
Muscular dystrophy (MD) is a group of over 30 genetic diseases that cause degeneration of skeletal muscles during voluntary movement and overall progressive weakness in muscle strength [23]. These diseases can be classified into nine major types including Duchenne, Becker, Myotonic, Congenital, Emery-Dreifuss, Facioscapulohumeral (FSHD), Limb-girdle,
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Journal of Veterinary Science & Animal Husbandry
ISSN: 2348-9790
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The role of MAPKs in dystrophy is not completely understood, and the inconclusive evidence from different diseases and experimental settings confounds a definitive role of MAPKs in the pathogenesis of muscular dystrophy [22]. Interestingly, a mechanistic link has been built between the dystrophin-glycoprotein complex (DGC), a structure that is dysfunctional in muscular dystrophy and the MAPK pathway. The DGC not only provides structural support to cells, but also bridges extracellular stimuli and intracellular reaction through specific physical interactions with intracellular proteins [30]. Some of these proteins, such as adapter protein Grb2, are involved in the MAPK signal transduction, which suggests that DGC may function to transduce signals through the MAPKs to maintain skeletal muscle fiber viability [22]. Our recent work on MAPK phosphatases (MKPs) has added another layer of regulation of MAPKs in Duchenne muscular dystrophy. MKP-1 is a nuclear phosphatase that dephosphrylates p38 MAPK, JNK, and ERK1/2 not only in skeletal muscle but also in the immune, metabolic, and nervous system as well [9,31-34]. In the cardiotoxin- induced skeletal muscle regeneration, knockout of MKP-1 impaired the recovery of the damaged muscle likely through the effect of p38 MAPK pathways on muscle stem cell function [33], since the precocious differentiation of muscle stem cells caused by enhanced p38 MAPK may slow down the injured muscle from returning to a normal musculature [33]. Interestingly, when another MKP family member MKP-5 was knocked out, muscle regeneration following damage was greatly improved [35]. When MKP-5 was knocked out in the mdx mouse, an animal model for Duchenne muscular dystrophy, the dystrophinopathy was ameliorated and muscle functions were restored [35]. The obvious discrepancy between MKP-1 and MKP-5 knockout studies can be explained by the fact that MKP-5 is both nuclear and cytosolic, though its substrates include p38 MAPK, JNK and ERK1/2, it functions on distinct pools of MAPKs from MKP-1 due to their subcellular localization [35]. Together, these findings suggest that MAPKs may play pivotal roles in the phathogenesis of muscular dystrophy, however, the definitive role of each MAPK in the network of signaling pathways that contribute to the progression of the diseases remains to be further investigated. MAPKs and Muscle Atrophy
Skeletal muscle atrophy is characterized by decrease in cell size through organelle, cytoplasm, and protein loss [36]. Biochemically, muscle atrophy is a result of negative balance between protein synthesis and degradation. This imbalance in protein turnover occurs during fasting, disuse of selected skeletal muscles, and a plethora of systemic diseases such as cancer, diabetes mellitus, AIDS, sepsis, and Cushing’s Syndrome [37].
Traditionally, it was thought there are two types of muscular atrophy in skeletal muscles: neurogenic atrophy and muscle atrophy through ubiquitin-dependent proteolysis [38]. Healthy muscle maintains its size, structure, and function through innvervation of motor neurons to skeletal muscle fibers, and through balance of protein accretion. Upon disruption of the nervous system, denervation occurs and neurogenic muscle atrophy ensues [38]. Such disorders are seen in amyotrophic lateral sclerosis (ALS), Guillain-Barré syndrome, polio, and polyneuropathy which ultimately leads to paralysis [38]. In contrast, ubiquitin-dependent proteolysis occurs during increased rate of protein degradation through the ubiquitin-proteasome pathway [39] and transcriptional adaptations called “atrophy program” [40]. Recently, emerging evidence indicates that there is another equally important protein breakdown machinery in skeletal muscle called autophagy-lysosome system. In mammals, there are three different types: macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy [41], though the mechanistic aspect of each category remains yet to be further defined.
Due to the fact that muscle atrophy occurs in a large number of diseases and disorders in both humans and animals, it is a focal point of interest in basic research and clinical investigation. In agriculture and veterinary medicine, muscle atrophy caused by malnutrition is the culprit of inefficiently growing animals and alters meat quality. Atrophy, along with caloric restriction, induces cytoskeletal remodeling of muscle fibers which may contribute to lower quality less tender meat product [42]. Aging also proves to be a factor for muscle atrophy. In the hindlimbs of older dogs, a growing insensitivity to adenosine triphosphate (ATP) occurs and muscle fibers undergo fibrosis which weakens muscle [43].
Among the various pathways that participate in the pathogenesis of muscle atrophy, MAPKs play a critical role. There are several lines of evidence that support this notion. First, when MKP-1, a phosphatase that dephosphorylates and thus inactivate MAPKs, was overexpressed in skeletal muscle fibers, it induced profound muscle fiber atrophy possibly through the ubiquitin-proteasome pathways [44]. This atrophic effect may be conferred through ERK1/2 signaling pathway, yet it does not exclude the possibility of a combined effect of ERK, JNK, and p38 MAPK pathways [44]. Second, given the fact that MAPKs play integral roles in innate immunity [45], it is reasonable to speculate that MAPK-mediated cytokine secretion may serve as an indirect effect on skeletal muscle atrophy as seen in chronic inflammation diseases. Specifically, activation of JNK and p38 MAPKs are involved in cytokine-induced
Distal, and Oculopharyngeal. The most common and severe muscular dystrophy is Duchenne muscular dystrophy (DMD) which accounts for greater than 50% of all disease cases. DMD is a prevalent muscular dystrophy in humans, affecting 1: 3,500 males in the United States [24]. Naturally occurring or spontaneous mutations in the DMD gene has been reported in Canine breeds such as Golden Retriever [25], German Short- Haired Pointer [26], and Cavalier King Charles[27]. Canine studies of X-linked DMD revealed that pups from an affected male were stunted on growth and showed progressive weakness and gait abnormalities which lead to muscle atrophy more over mine over they also exhibited fibrosis and contractures by 6 months of age. Smaller breeds are less affected than large crosses [28]. In feline DMD models, the disorder is referred to as hypertrophic feline muscular dystrophy (HFMD) due to a loss of dystrophin in skeletal and heart muscles, skeletal muscle hypertrophy occurs especially in the tongue muscles [29].
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Journal of Veterinary Science & Animal HusbandryFuture Perspectives
A wealth of data supports a critical role of the MAPKs in the pathogenesis of skeletal muscle diseases. MAPKs are activated and inactivated in a temporal and spatial manner through their upstream kinases and a family of phosphatases to achieve specific biological responses. Research in this area has begun to shed a light on the complexity and hierarchy of the MAPK regulation and how this signaling pathway is integrated into the intertwined signaling network system within a cell. Knockout animal models targeting specific MAPKs and their isoforms are useful tools to define the role of each individual MAP kinase in a specific muscle disease. Although mice are an excellent model to study the mechanistic insight of the MAPK in muscle diseases, other animal models are valuable especially in veterinary medicine and agriculture. Large animals may be more challenging for gene manipulation, yet the work in pigs has brought promise for the use of large animals to study human diseases. Animals with spontaneous mutations in genes of interest are another valuable tool to study muscle diseases. In all, research in the MAPK pathway will undoubtedly broaden our understanding of the etiology and pathogenesis of muscle disease and the molecular signatures that define the pathological process. All of these efforts are targeted to develop therapeutic means to improve the health of humans and animals. Given the fact that MAPK signaling pathway is ubiquitous in all cell types, drugs that inhibit MAPK signaling may have undesired effects. As such, identification of the downstream effectors of the MAPKs that convey MAPK effects in a specific disease will be an optimal choice.
3. Whitmarsh AJ (2006) The JIP family of MAPK scaffold proteins. Biochem Soc Trans 34: 828-832.
4. Zarubin T, Han J (2005) Activation and signaling of the p38 MAP kinase pathway. Cell Res 15: 11-18.
5. Lawan A, Shi H, Gatzke F, Bennett AM (2013) Diversity and specificity of the mitogen-activated protein kinase phosphatase-1 functions. Cell Mol Life Sci 70: 223-237.
6. Wancket LM, Frazier WJ, Liu Y (2012) Mitogen-activated protein kinase phosphatase (MKP)-1 in immunology, physiology, and disease. Life Sci 90: 237-248.
7. Cuevas BD, Abell AN, Johnson GL (2007) Role of mitogen-activated protein kinase kinase kinases in signal integration. Oncogene 26: 3159-3171.
8. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, et al. (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22: 153-183.
9. Boutros T, Chevet E, Metrakos P (2008) Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer. Pharmacol Rev 60: 261-310.
10. Duan W, Wong WS (2006) Targeting mitogen-activated protein kinases for asthma. Curr Drug Targets 7: 691-698.
11. Jeffrey KL, Camps M, Rommel C, Mackay CR (2007) Targeting dual- specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov 6: 391-403.
12. Dong C, Davis RJ, Flavell RA (2002) MAP kinases in the immune response. Annu Rev Immunol 20: 55-72.
13. Jeanneteau F, Deinhardt K, Miyoshi G, Bennett AM, Chao MV (2010) The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nat Neurosci 13: 1373-1379.
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