Protein Kinase C-Dependent Increase in Reactive Oxygen Species Production in Vascular Tissues of Diabetes: Role of Vascular NAD(P)H Oxidase Qian Lingbo 05.06.17
Qian Lingbo 05.06.17 Protein Kinase C–Dependent Increase in Reactive Oxygen Species Production in Vascular Tissues of Diabetes: Role of Vascular NAD(P)H Oxidase 1
Background h ECs Cellular response to ROS NO ONOO≤ NOS *02 Impaired relaxation Angiogenesis Apoptosis Monocyte adhesion Hypertension Oxidation Damage MPO Atherosclerosis of HaB Hypertrophy DM Vasculopathy Proliferation Restenosis Short of L-arginine or NAD(P)H oxidas ◆0 H,O, Migration HB Matrix requlation VSMCs Activated cells Cytokine production/ aicalstretch Pathological circumstances Effects of ROS on Vascular Cells
ONOO- NO O2 NOS -. Short of L-arginine or H4B Oxidation of H4B Pathological circumstances Damage Effects of ROS on Vascular Cells Background 2
DIABETES PKC+HYPERGLYCEMIA AGEs ROS Catalase Mr:Ec Peroxidase 一→oo NO H07 HONO o LONO LOO" LOONO MPO HOC ROS O OXIDATIVE STRESS Major ROS in diabetic processes 3
Major ROS in diabetic processes 3
Diabetes Diabeticvascular complication EDVD Atherosclerosis (Hypertension etc Hyperglycemia ROS PKC Note:PKC-B is more important in diabetic vascular damages
EDVD Atherosclerosis Hypertension Hyperglycemia ROS PKC ? etc. Note: PKC- is more important in diabetic vascular damages Diabetes Diabeticvascular complication 4
PKC-dependent activation of NAD(P)H oxidase may be an essential mechanism for increased ROS in diabetic vessels Diabetic state diacylglycerol(DAG)-protein kinase C(PKC)pathway NAD(P)H oxidase t Vascular damage ROS
diacylglycerol (DAG)-protein kinase C (PKC) pathway Diabetic state NAD(P)H oxidase ROS Vascular damage PKC-dependent activation of NAD(P)H oxidase may be an essential mechanism for increased ROS in diabetic vessels 5
Activation of PKC in Diabetic Vascular Tissues 0000 MEMBRANE CYTOSOLIC 8000 n=4 CYTOSOL MEMBRANE 6000 5522 PMA 5.522 PMA GLUCOSE GLUCOSE 2000 BI 5.522 PMA 5522 MA C DM Ins C DM Ins
6 Activation of PKC in Diabetic Vascular Tissues
200 endothelial cells AORTA 1。 Glucose Conc.5.5 22 (mM) smooth muscle cells 6 ol C DM INS 5.5 22
7
PKC-Dependent Activation of NAD(P)H Oxidase Induced by High Glucose aortic smooth muscle cells aortic endothelial cells 141x102 P<0.001 Pc0.001 1x10-2 Pc0.001 12 c0.01 uo 8
aortic smooth muscle cells aortic endothelial cells PKC-Dependent Activation of NAD(P)H Oxidase Induced by High Glucose 8
Effect of STZ treatment on NAD(P)H oxidase activity(A)and on the NAD(P)H oxidase subunit mRNA gp91phox(B) IMA non-DM DM A x p22p NAD(P)H oxidase protein Control STZ-treated subunits in human diabetes Internal mammary arteries(IMA) and saphenous veins (HSV) 9
Effect of STZ treatment on NAD(P)H oxidase activity (A) and on the NAD(P)H oxidase subunit mRNA gp91phox (B) NAD(P)H oxidase protein subunits in human diabetes Internal mammary arteries (IMA) and saphenous veins (HSV) 9
molecular mechanism High glucose Rac-1 PKC inhibitors NAD(P)H oxidase 10
molecular mechanism High glucose Rac-1 PKC inhibitors NAD(P)H oxidase Ros 10