《通过葡萄糖诱导氧化应激，刺激血管内皮细胞中的NADPH氧化酶4活性和表达的增加.ppt》由会员分享，可在线阅读，更多相关《通过葡萄糖诱导氧化应激，刺激血管内皮细胞中的NADPH氧化酶4活性和表达的增加.ppt（24页珍藏版）》请在三一文库上搜索。
1、Increased activity and expression of NADPH oxidase 4 stimulated by glucose induces oxidative stress in vascular endothelial cells Jian LI Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China,-cell,liver,obesity,-Cell Dysfunction,Insulin Resistance,
2、FFA VLDL,FFA VLDL,Glucose,Oxidative stress,Hypothesis,Redox “rheostat“ in cells,Where are reactive oxygen species generated?,Mitochondrial respirtion-chain enzyme complex xanthine oxidase, NOS, lipoxygenase Phagocyte NADPH oxidase NADPH oxidase of non-phagocytic cells NADPH oxidase is a major source
3、 of vascular ROS production.,NOX-type NADPH oxidases as superoxide-producing enzymes,Structure of the NADPH oxidase,The NOX family of NADPH oxidases,gp91phox homology,EF-hands,Nox1 colon Nox2 phagocytes Nox3 inner ear Nox4 kidney and vascular cells,Nox5 testis and lymphoid tissues,O2,O2-,NADPH,e-,A,
4、B,C,D,DPI:NOX inhibitor; Rotenone: inhibitor of mitochondrial respirtion-chain enzyme complex; L-NAME:NOS inhibitor; Oxypurinol: xanthine oxidase inhibitor,NADPH oxidase is a major source of vascular ROS production induced by glucose,A: negative control; B: HUVEC; C: 20mM glucose treated HUVEC; D: p
5、ositive control,Glucose induces apoptosis of HUVEC,C:HUVEC; G:20mM glucose-treated HUVEC,Western blot,Glucose up-regulates the expression of NOX4,M A N1 N2 N3 N4 p22 p47 p67 Rac1,RT-PCR,0 10 20 30 glucose(mM),A: negative control; B: transfected with GFP-pcDNA3.1; C: transfected with NOX4-pcDNA3.1,Ov
6、er-expression of NOX4 increases the level of ROS and results in apoptosis,NOX4-siRNA decreases the expression of NOX4 and the level ROS in HUVEC,*,*,*,*,*,*,Mechanism for increased ROS production induced by diabetes and insulin-resistant state,Diabetes,High glucose level,Insulin resistance Obesity,E
7、levated NEFA level,De novo DAG synthesis,Vascular cells,PKC activation,NADPH oxidase activation,Superoxide ROS,Activation of NADPH oxidase,Immunoflurescence staining of p47phox,PKC/p47phox regulates the activation of NOX4,ROS level,ROS level,Schematic illustration of ROS-mediated NFB activation,Gluc
8、ose activates NFB pathway,C G,C,G,G+DPI,NFB,DAPI,Merge,C G G+SB,Glucose activates p38MAPK pathway,C G G+SB203580,Western blot,Hochest/PI staining,Immunofluorescence,C G G+SB203580,Anti-oxidation agents for the oxidative damage of vascular endothelial cells,high glucose level,PKC activation,PKC inhib
9、itor,Angiotensin II,NAD(P)H oxidase activation,Statins,ARB ACEI,HDL,Probucol,Simvastatin decreases the level of MDA and TG in the atherosclerosis model of apo E-/- mice,*,MDA,TC,TG,SOD,*,*,Simvastatin suppresses the generation of ROS and expression of NOX in atherosclerotic plaque,control,Simvastatin treatment,ROS,NOX2,p47PHOX,NOX4,Simvastatin has the ability to stabilize the vulnerable atherosclerotic plaque,control,Simvastatin treatment,The area of AS lesion,The thickness of fibrous cap,The content of collagen,Thank you!,