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Peroxisomes in dermatology.ppt
- 23. PPAR:RXR Co-repressors Co-activators Modulation of gene transcription ? ? ? Biological effect Mechanism of PPAR action RXR Ligands PPAR Ligand
- 24. Mechanism of PPAR action
- 31. Biological roles of PPAR PPAR mediates the induction of multiple enzymes required to mobilize and transport fatty acids from adipose stores to liver for catabolism. Basis for therapeutic use in humans to lower serum lipids.
- 32. Biological roles of PPAR / Ligand activation of PPAR / leads to terminal differentiation of keratinocytes as shown by four independent laboratories. Activation of PPAR / in skeletal muscle leads to increased catabolism of fatty acids and improved insulin sensitivity.
- 33. Biological roles of PPAR The role of PPAR in carcinogenesis is also controversial. There is evidence that activation of PPAR can either potentiate or attenuate cancer, but current consensus favors attenuation.
- 34. Orchestration of Immune Responses TISSUES Thymus Spleen Lymph nodes Blood CELLS Lymphocytes Monocytes/Macs Neutrophils Eosinophils Basophils Dendritic cells MOLECULES Complement Lysozyme Inflammatory mediators Chemokines Cytokines Innate immunity Adaptive Immunity PPARs are found in a number of immune cell types and there is evidence that they could modulate a number of different immune responses
- 68. THANK YOU
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- Depending on developmental stage and environment, #, size, enzymes, metabolic function, varies. Grow on sugar: small peroxisomes Grow on methanol: large peroxisomes that oxidize methanol Grow on FA: large and break down FA to AcetylCoA by -oxidation
- Peroxisome proliferator-activated receptors (or PPARs) are members of the steroid receptor superfamily and were cloned only recently in the early 1990s. Three subtypes have been identified including , , and , each encoded by a separate gene and exhibiting unique tissue distribution. For example, PPAR is found in high concentration in the liver, and as I will show you today has roles in both lipid metabolism and carcinogenesis. In contrast, PPAR is ubiquitously expressed and no function for this receptor has been identified. PPAR is found extensively in adipocytes and has been found to be involved in adipocyte differentiation.
- As I eluded to, PPAR-dependent transcriptional regulation is actually a lot more complex than the previous slide. As shown in this slide, there are numerous sites that may be regulated including the presence or absence of ligands/activators, as well as intracellular levels of co-activators and co-repressors which may be different in different tissues. Once all of these regulatory mechanisms have been elucidated, we’ll have a more clear understanding of the diverse roles for the PPARs.
- As I eluded to, PPAR-dependent transcriptional regulation is actually a lot more complex than the previous slide. As shown in this slide, there are numerous sites that may be regulated including the presence or absence of ligands/activators, as well as intracellular levels of co-activators and co-repressors which may be different in different tissues. Once all of these regulatory mechanisms have been elucidated, we’ll have a more clear understanding of the diverse roles for the PPARs.
- As I eluded to, PPAR-dependent transcriptional regulation is actually a lot more complex than the previous slide. As shown in this slide, there are numerous sites that may be regulated including the presence or absence of ligands/activators, as well as intracellular levels of co-activators and co-repressors which may be different in different tissues. Once all of these regulatory mechanisms have been elucidated, we’ll have a more clear understanding of the diverse roles for the PPARs.
- As I eluded to, PPAR-dependent transcriptional regulation is actually a lot more complex than the previous slide. As shown in this slide, there are numerous sites that may be regulated including the presence or absence of ligands/activators, as well as intracellular levels of co-activators and co-repressors which may be different in different tissues. Once all of these regulatory mechanisms have been elucidated, we’ll have a more clear understanding of the diverse roles for the PPARs.
- As I eluded to, PPAR-dependent transcriptional regulation is actually a lot more complex than the previous slide. As shown in this slide, there are numerous sites that may be regulated including the presence or absence of ligands/activators, as well as intracellular levels of co-activators and co-repressors which may be different in different tissues. Once all of these regulatory mechanisms have been elucidated, we’ll have a more clear understanding of the diverse roles for the PPARs.