[医药卫生]氧化应激与糖尿病OxidativestressandDiabetes.pptVIP

Oxidative Stress and Diabetes Jian Li Beijing Institute of Geriatrics Ministry of Health Reactive oxygen species (= ROS) killing of microorganisms DNA damage cancerogenesis ageing cell death NO inactivation and peroxynitrite generation NOX-type NADPH oxidasesas superoxide-producing enzymes The NOX family of NADPH oxidases NAD(P)H Oxidase Activation  nonatherosclerotic arteries atherosclerotic arteries Thank you! * Redox rheostat“ in vascular cells O2 O2- H2 O2 acidic pH, Superoxyde Dismutase (SOD) NADPH oxidase Superoxide anion Hydrogen peroxide Proposed functions of ROS regulation of cell growth and differentiation regulation of cell function oxygen sensing activation of redox-sensitive transcription factors activation of redox-sensitive second messenger systems Where and why are reactive oxygen species generated? Mitochondria by-product of the oxidative metabolism Phagocyte NADPH oxidase microbial killing NADPH oxidase of non-phagocytic cells cell growth, cell signaling Fe Fe outside inside I VI IV II III V NH2 H H H H H H NADPH FAD COOH H115 O2 O2- e- Review: Lambeth et al. Novel homologs of gp91phox.Trends in Biochemical Sciences 25: 459-461, 2000. gp91phox homology EF-hands Nox1 colon Nox2 phagocytes Nox3 inner ear Nox4 kidney Nox5 testis and lymphoid tissues O2 O2- NADPH e- Structure of the NAD(P)H oxidase Characteristics of neutrophil and vascular NAD(P)H oxidase Adenovirus-induced overexpression of PKC-β2 causes the membranous translocation of p47phox and p67phox A model illustrating how increased ROS production in accumulated fat contributes to metabolic syndrome Mechanism for increased ROS production induced by diabetes and insulin-resistant state Linking various risk factors to ROS generation in the development of IDDM Initiation and amplification of the immune/inflammatory response by ROS-induced NFκ B activation in β-cell death Schematic illustration of RO