Effect of Amifostine On Effect of Amifostine On Mitochondrial Superoxide Mitochondrial Superoxide Dismutase Expression In Dismutase Expression In INS-1 Beta Cells INS-1 Beta Cells Daniel Turner-Lloveras Daniel Turner-Lloveras Dr. Michael Roe Dr. Michael Roe
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Effect of Amifostine On Mitochondrial Superoxide Dismutase Expression In INS-1 Beta Cells
Effect of Amifostine On Mitochondrial Superoxide Dismutase Expression In INS-1 Beta Cells. Daniel Turner-Lloveras Dr. Michael Roe. Type 2 Diabetes Mellitus. Insulin Resistance Beta Cell Dysfunction Hyperglycemia Oxidative Stress (ROS) Beta Cell Degradation Beta Cell Death - PowerPoint PPT Presentation
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Effect of Amifostine On Effect of Amifostine On Mitochondrial Superoxide Mitochondrial Superoxide Dismutase Expression In Dismutase Expression In
Enhanced Endogenous Enhanced Endogenous Antioxidant Defense during Antioxidant Defense during
hyperglycemiahyperglycemia??
O2- H2O2
Catalase(?)
HIGH [GLUCOSE]
(high mitochondrialmetabolic activity)
HypothesisHypothesis
• Amifostine induces upregulation of Amifostine induces upregulation of MnSOD (Sod2) via activation of NF-MnSOD (Sod2) via activation of NF-κβκβ
AmifostineAmifostine
• A phosphorothioate that is A phosphorothioate that is metabolized to the free thiol metabolized to the free thiol metabolite WR-1065.metabolite WR-1065.
• Developed by military to protect Developed by military to protect soldiers during nuclear warfare.soldiers during nuclear warfare.
• The only drug approved by the The only drug approved by the FDA specifically as a FDA specifically as a radioprotector.radioprotector.
• Effects on MnSOD protein levels Effects on MnSOD protein levels are uncertain.are uncertain.
Future DirectionsFuture Directions
• Refine Technique and repeat Refine Technique and repeat experimentsexperiments
• Investigate role of NF-Investigate role of NF-κκBB• Mitochondrial function and insulin Mitochondrial function and insulin
secretionsecretion• In vivoIn vivo experiments with Fatty experiments with Fatty
Zucker Diabetic RatsZucker Diabetic Rats
AcknowledgementsAcknowledgements
• Dr. Michael RoeDr. Michael Roe• Dr. David GrdinaDr. David Grdina• Dr. Jeff MurleyDr. Jeff Murley• Luis LandaLuis Landa• Dr. Mark HarbeckDr. Mark Harbeck• Kelly KaiharaKelly Kaihara• Dr. Kajorn Kitiphongspattana Dr. Kajorn Kitiphongspattana • Dr. Vernon TowleDr. Vernon Towle• Dr. Eugene ChangDr. Eugene Chang