The document summarizes key aspects of apoptosis including:
- The origins and definition of the term apoptosis from Greek meaning "falling leaves".
- The significance of apoptosis in development and maintenance of tissues by removing excess or damaged cells.
- The morphological features of apoptosis including membrane blebbing, nuclear fragmentation, and formation of apoptotic bodies.
- The molecular mechanisms including caspase signaling pathways like the intrinsic pathway involving mitochondria and the extrinsic pathway involving death receptors.
- Regulatory mechanisms involving proteins like Bcl-2 that balance survival and death signals.
- Dysregulation of apoptosis can lead to diseases like cancer, autoimmune disorders, and HIV infection.
Content-
1. Background
2. Introduction
3. Difference between apoptosis and necrosis
4. Apoptosis in biologic processes
5. Apoptosis in pathologic processes
6. Morphologic features
7. Techniques to identify and count apoptotic cells
8. Biochemical changes
9. Molecular mechanism of apoptosis
10. Recent advancement and emerging trends in apoptosis
11. References
Apoptosis also known as cell suicide. Difference between necrosis and apoptosis. Changes in apoptosis. Mechanism of apoptosis. Functional significance of apoptosis. Applied aspects of apoptosis
Cell death, particularly apoptosis, is probably one of the
most widely-studied subjects among cell biologists.
Understanding apoptosis in disease conditions is very
important as it not only gives insights into the pathogenesis
of a disease but may also leaves clues on how
the disease can be treated. In cancer, there is a loss of
balance between cell division and cell death and cells
that should have died did not receive the signals to do
so. The problem can arise in any one step along the way
of apoptosis.Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions.
It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of
apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due
to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the
culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not
die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along
these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to
anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of
cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting
apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment
strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely
in human subjects.. It is used,
in contrast to necrosis, to describe the situation in
which a cell actively pursues a course toward death
upon receiving certain stimule
Content-
1. Background
2. Introduction
3. Difference between apoptosis and necrosis
4. Apoptosis in biologic processes
5. Apoptosis in pathologic processes
6. Morphologic features
7. Techniques to identify and count apoptotic cells
8. Biochemical changes
9. Molecular mechanism of apoptosis
10. Recent advancement and emerging trends in apoptosis
11. References
Apoptosis also known as cell suicide. Difference between necrosis and apoptosis. Changes in apoptosis. Mechanism of apoptosis. Functional significance of apoptosis. Applied aspects of apoptosis
Cell death, particularly apoptosis, is probably one of the
most widely-studied subjects among cell biologists.
Understanding apoptosis in disease conditions is very
important as it not only gives insights into the pathogenesis
of a disease but may also leaves clues on how
the disease can be treated. In cancer, there is a loss of
balance between cell division and cell death and cells
that should have died did not receive the signals to do
so. The problem can arise in any one step along the way
of apoptosis.Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions.
It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of
apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due
to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the
culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not
die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along
these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to
anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of
cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting
apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment
strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely
in human subjects.. It is used,
in contrast to necrosis, to describe the situation in
which a cell actively pursues a course toward death
upon receiving certain stimule
Caspases are a family of cysteine proteases that serve as primary effectors during apoptosis to proteolytically dismantle most cellular structures, including the cytoskeleton, cell junctions, mitochondria, endoplasmic reticulum,
A detailed description of programmed cell death mechanism also called Apoptosis.
It explains about the factors, mechanism and pathways involved in the apoptosis.
Hi! I am Komal Sankaran, M.Sc. Biotechnology (Pune University Gold Medalist, 2013), CSIR-NET SPM fellow (Jun- 2014, 4th rank), CSIR-NET- LS (Dec 2013, 2nd rank), DBT JRF category- I. Please contact if anyone is interested in Life Sciences CSIR-NET coaching in Pune (Khadki area).
Email- komalsan91@gmail.com
Introduction
Definition
History
Evolution and origin of apoptosis
Significance
Purpose of apoptosis
Steps /process
Morphological and biochemical changes
Mechanism of apoptosis
Caspases
Regulation of apoptosis
Disorders of apoptosis
Application
Conclusion
Referances
Caspases are a family of cysteine proteases that serve as primary effectors during apoptosis to proteolytically dismantle most cellular structures, including the cytoskeleton, cell junctions, mitochondria, endoplasmic reticulum,
A detailed description of programmed cell death mechanism also called Apoptosis.
It explains about the factors, mechanism and pathways involved in the apoptosis.
Hi! I am Komal Sankaran, M.Sc. Biotechnology (Pune University Gold Medalist, 2013), CSIR-NET SPM fellow (Jun- 2014, 4th rank), CSIR-NET- LS (Dec 2013, 2nd rank), DBT JRF category- I. Please contact if anyone is interested in Life Sciences CSIR-NET coaching in Pune (Khadki area).
Email- komalsan91@gmail.com
Introduction
Definition
History
Evolution and origin of apoptosis
Significance
Purpose of apoptosis
Steps /process
Morphological and biochemical changes
Mechanism of apoptosis
Caspases
Regulation of apoptosis
Disorders of apoptosis
Application
Conclusion
Referances
Apoptosis is a
-pathway of cell death that is
-induced by an internally regulated program
-in which cells destined to die activate intrinsic enzymes that --degrade the cells’ own nuclear DNA and also nuclear and cytoplasmic proteins
-With minimal host reaction.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. Content:
• The development of the term
Apoptosis
• The significance of Apoptosis
• Morphological features of
apoptosis
• Molecular mechanisms of apoptosis
signalling pathways.
• Regulatory mechanisms in
apoptosis signal
• Disease as a consequences of
dysregulated apoptosis.
3. APOPTOSIS
Greek word : Falling leaves (like in Autumn)
In the human body about 100,000 cells are produced every
second by mitosis and a similar number die by apoptosis !!!
4. • The word "apoptosis" (ἁπόπτωσισ) is used in Greek
to describe the "dropping off" or "falling off" of
petals from flowers, or leaves from trees.
• The second half of the word being pronounced like
"ptosis" (with the "p" silent), which comes from the
same root "to fall“
• The term programmed cell death was introduced in
1964, proposing that cell death during development
is not of accidential nature but follows a sequence of
controlled steps leading to locally and temporally
defined self-destruction.
DEVELOPMENT OF WORD APOPTOSIS
5. History
• Apoptotic principle was first described by
KARL VOGT in 1842
• “APOPTOSIS” term was coined by JAMES
CORMACK
• 2002 NOBEL PRIZE IN MEDICINE was awarded
to SYDNEY BRENNER,HORVITZ and
JOHN.E.SULSTON for their work in identifying
genes that control Apoptosis.
John E Sulton won Nobel
Prize in 2002 for his
pioneering research in
Apoptosis
6. History of cell death / apoptosis research
1800s Numerous observation of cell death
1908 Mechnikov wins Nobel prize (phagocytosis)
1930-40 Studies of metamorphosis
1948-49 Cell death in chick limb & exploration of NGF
1955 Beginning of studies of lysomes
1964-66 Necrosis & PCD described
1971 Term apoptosis coined
1977 Cell death genes in C. elegans
1980-82 DNA ladder observed & ced-3 identified
1989-91 Apoptosis genes identified, including bcl-2,
fas/apo1 & p53, ced-3 sequenced
7. SIGNIFICANCE OF APOTOSIS
• The development and maintenance of multicellular
biological systems depends on a sophisticated
interplay between the cells forming the organism, it
sometimes even seems to involve an altruistic
behaviour of individual cells in favour of the
organism as a whole.
• During development many cells are produced in
excess which eventually undergo programmed cell
death and thereby contribute to sculpturing many
organs and tissues
8. An orderly
disposal of cells
that need to die
DNA has
sustained too
many injuries
Cell is infected
with a virus
Cell needs to
be removed for
body parts to
be formed
Cell is just too
old and ’ its time
has come’
9. Apoptosis is needed for proper development
Examples:
The resorption of the tadpole tail
The formation of the fingers and toes of the fetus
The sloughing off of the inner lining of the uterus
The formation of the proper connections between
neurons in the brain
Apoptosis is needed to destroy cells
Examples:
Cells infected with viruses
Cells of the immune system
Cells with DNA damage
Cancer cells
14. Bleb
Blebbing & Apoptotic bodies
The control retained over the cell membrane
& cytoskeleton allows intact pieces of the cell
to separate for recognition & phagocytosis by
MFs
Apoptotic body
MF MF
16. Molecular mechanisms of apoptosis
signalling pathways
• What makes a cell commit suicide?
• withdrawal of positive signals (growth factors, Il-2)
• receipt of negative signals (increased levels of oxidants, DNA
damage via X-ray or UV light, chemotherapeutic drugs,
accumulation of improperly folded proteins, death activators
such as: TNF-a, TNF-b, Fas/FasL)
• Steps in apoptosis:
– the decision to activate the pathway;
– the actual "suicide" of the cell;
– engulfment of the cell remains by specialized immune
cells called phagocytes;
– degradation of engulfed cell.
18. Four stages of apoptosis have been defined:
i. Commitment to death by extracellular or intracellular triggers/signals
ii. Cell killing (execution) by activation of intracellular proteases (caspases)
iii. Engulfment of cell corpse by other cells
iv. Degradation of the cell corpse within the lysosomes of phagocytic cells
19. Caspases are a family of aspartate-specific, cysteine
proteases that serve as the primary mediators of apoptosis.
Mammalian caspases can be subdivided into three functional
groups, apoptotic initiator caspases (Caspase-2, -8, -9, -10),
apoptotic effector caspases (Caspase-3, -6, -7), and caspases
involved in inflammatory cytokine processing (Caspase-1, -4,
-5, 11, and -12L/12S). All caspases are synthesized as inactive
zymogens containing a variable length pro-domain, followed
by a large (20 kDa) and a small (10 kDa) subunit.
Caspases
20.
21.
22. Stimuli for Apoptotic Cell Death in Mammals
i. Growth factor deficiencies
ii. Ionizing radiation/ viral infection
iii. Free radical toxicity
iv. Death receptor activation (such as Fas or CD95
triggering)
v. Metabolic or cell cycle disturbance
26. Ligand-induced cell death
“The death receptors”
Ligand-induced trimerization
Death Domains
Death Effectors
Induced proximity
of Caspase 8
Activation of
Caspase 8
FasL
Trail
TNF
27.
28.
29. Intracellular signals
Oxidative damage from free radicals, Radiation, Virus infection, Nutrient deprivation,
Pro-apoptotic Factors
Damage to the mitochondrial membrane increasing permeability
Entry of Cytochrome C into the cytoplasm
Cytochrome C binds to Apaf-1 forming an apoptosome
Apoptosome activates procaspase-9 to caspase-9
Caspase-9 cleaves and activates caspase-3 and caspase-7.
This executioner caspases activate a cascade of proteolytic activity that leads to:
Chromatin condensation, DNA fragmentation, Protein cleavage, Membrane
permeability
32. Granzyme mediated apoptosis
Granzymes are serine proteases that are released by cytoplasmic
granules within cytotoxic T cells and natural killer (NK) cells.
They induce programmed cell death in the target cell, thus
eliminating cells that have become cancerous or are infected
with viruses or bacteria. The granzymes also kill bacteria[ and
inhibit viral replication. In NK cells and T cells, the granzymes are
packaged in cytotoxic granules with perforin Other locations that
granzymes can be detected are in the rough endoplasmic
reticulum, golgi complex, and the trans-golgi reticulum. The
contents of the cytotoxic granules function to permit entry of
the granzymes into the target cell cytosol. The granules are
released into an immune synapse formed with a target cell,
where perforin mediates the delivery of the granzymes
into endosomes in the target cell, and finally into the target cell
cytosol. Granzymes are identified as being part of the serine
esterase family.[3]
33.
34.
35. Cells are balanced between life and death
DAMAGE Physiological death signals
DEATH SIGNAL
PROAPOPTOTIC
PROTEINS
(dozens!)
ANTIAPOPTOTIC
PROTEINS
(dozens!)
DEATH
36. Regulation of apoptosis
Regulatory proteins – BCL -2
Bcl2 was the first apoptosis-related gene ,recognized to play a role tumor genesis
BCL-2 is a human proto-oncogene located on chromosome 18.
Its product is an integral membrane protein (called Bcl-2) located in the membranes of the
endoplasmic reticulum , nuclear envelope, and in the outer membrane of mitochondria.
The gene was discovered as the translocated locus in a B-cell leukemia (hence the name).
This translocation is also found in some B-cell lymphomas
37.
38.
39. How pro-apoptotic BH3-only and anti-apoptotic Bcl2 proteins regulate
the intrinsic pathway of apoptosis
39
40. • Extracellular signal molecules that inhibit
apoptosis which are collectively called survival
factors.
• Most animal cells require continues signaling
from other cells to avoid apoptosis.
• Nerve cells are produced in excess in the
developing nervous system and then compete for
limited amount of survival factors that are
secreted by the target cells that they normally
connect to .
Extracellular survival factors inhibit apoptosis in various ways
40
41. • Nerve cells that receive enough of the
appropriate type of survival signal live, while the
others die.
41
43. Apoptosis and Cancer
• Apoptosis does not occur in
Cancer
• Cancerous cells trick and skip
Apoptosis in number of ways
Inactivation of p53 [shooting the
guard]
Produce Bcl-2 or a protein which
mimics Bcl-2
Inhibits expression of Apaf-1
44. Apoptosis and Autoimmune
Disease
Autoimmune Lymph
Proliferative
Syndrome[ALPS]
Apoptosis doesnot
occur in self
reactive T & B cells
RBC
Hemolytic
Anemia
Neutrophil
Neutrope
nia
Platelets
Thromboc
ytopenia
45. Apoptosis and HIV
Infected CD4
cell induces
Apoptosis in
surrounding
cells
• Deactivated Bcl-2
• Decreases CD4
Glycoprotein
markers on
innocent T cells
,getting them
killed
Infected CD4 cell
avoids Apoptosis in
itself
Decreases
Phosphatdylserine
marker for itself
allowing longer
survival.
46. Overview
Apoptosis is a good thing
Too little of a good thing
is bad [Cancer]
Too much of a good
thing is also bad [HIV]
47. REFERENCES
1. JORGE EDUARDO DUQUE-PARRA. Note on the Origin
and History of the Term“Apoptosis”. THE ANATOMICAL
RECORD (PART B: NEW ANAT.) 283B:2–4, 2005.
2. Hans JR,Doris E. Apoptosis, Cytotoxicity and Cell
Proliferation.ROCHE2008:4;2-16.
3. Andreas G. ApoReview - Introduction to Apoptosis
2003;1-26
4. Min W,Han FD,David EF.Apoptosis :molecular
mechanism. ENCYCLOPEDIA OF LIFE SCIENCES / &
2001 Nature Publishing Group / www.els.net;1-8
5. The molecular biology of cell by Albert,
Johnson,Lewis. 5th edition ;1115-28.
