Hypoxia in periodontal disease
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Hypoxia in periodontal disease
- 1. RESPONSE TO HYPOXIA in PERIODONTAL TISSUES Dr R Viswa Chandra
- 2. Hypoxia- Less O2% Hypoxemia- Less PaO2% Ischemia- Lack of perfusion Dysoxia- Tissues inability to utilize oxygen Hypoxia-response elements (HREs) Target genes, RNA-binding proteins (RBPs) Hypoxia-response proteins (HRPs) GLUT1 and VEGF
- 4. HIF-1: HYPOXIA INDUCIBLE FACTOR - 1 1. HIF-1 is a protein with DNA binding activity. 2. Ubiquitous Expression 3. HIF-1 is a transcription factor that turns on genes needed for survival under hypoxic conditions. Oxygen Concentration
- 5. HIF-1 Target Genes Erythropoeitin (EPO) Nitric oxide synthase 2 (NOS2) Transferrin Transferrin receptor Vascular endothelial growth factor (VEGF) VEGF receptor FLT-1 O2 Delivery
- 6. HREs HRPs Hypoxia Recognition Hypoxia Response 1. RBPs and microRNAs that interact with HIF-1α mRNA and modulate the production of HIF-1α protein in hypoxia 2. HIF-1α transcriptionally upregulates the expression of target genes bearing HREs 3. Hypoxia-response proteins like GLUT1 and VEGF are transcripted
- 7. 1. With hypoxia, the HIF restored perfusion also facilitates PMNs’ diapedesis 2. Naturally occurring low-grade hypoxic reaction and hence HIF-1 accumulation in oral epithelia followed by corresponding HIF-1 downstream genes expression were recently postulated to be a key concept 3. Putative HIF-1α binding site prevented hypoxia- induced RANKL transcriptional promotion, thus suggesting that HIF-1α mediates hypoxia- induced upregulation of RANKL expression and enhanced osteoclastogenesis
- 8. What is the role of HIF-1 in periodontal surgery? What is the effect of periodontopathic organisms on HIF-1? What are the other Hypoxia- response elements seen in periodontal tissues? ?
- 9. THANK YOU
Editor's Notes
- Hypoxia Hypoxemia Ischemia Dysoxia Glucose transporter 1 GLUT1 facilitates the transport of glucose across the plasma membranes of mammalian cells. These processes are modulated efficiently by both RNA-binding proteins (rbpS))
- HIF is a transcription factor. Transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. HIF-1 expression increases exponentially when O2 concentration decreases. The curve shows a point of inflection around 4-5% O2, which is the O2 concentration in normal human tissues.
- Transferrin is a blood-plasma glycoprotein, which plays a central role in iron metabolism and is responsible for ferric-ion delivery Nitric oxide synthase is expressed in epithelial cells of the liver, lung and bone marrow. Nitric oxide is a reactive free radical mediating in neurotransmission, antimicrobial and antitumoral activities. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis
- A microRNA (abbreviated miRNA) is a small non-coding RNA. HIF-1 accumulates and translocates into nucleus. In the nucleus, it binds to HIF-1 forming HIF-1.