Impairment of mitochondrial respiratory chain activity in aortic endothelial cells induced by glycated low-density lipoprotein.
Coronary artery disease (CAD) is the leading cause of mortality in diabetic patients. Mitochondrial dysfunction and increased production of reactive oxygen species (ROS) are associated with diabetes and CAD. Elevated levels of glycated LDL (glyLDL) were detected in patients with diabetes. Our previous studies demonstrated that glyLDL increased the generation of ROS and altered the activities of antioxidant enzymes in vascular endothelial cells (EC). This study examined the effects of glyLDL on oxygen consumption in mitochondria and the activities of key enzymes in the mitochondrial electron transport chain (ETC) in cultured porcine aortic EC. The results demonstrated that glyLDL treatment significantly impaired oxygen consumption in Complexes I, II/III, and IV of the mitochondrial ETC in EC compared to LDL or vehicle control detected using oxygraphy. Incubation with glyLDL significantly reduced the mitochondrial membrane potential, the NAD(+)/NADH ratio, and the activities of mitochondrial ETC enzymes (NADH-ubiquinone dehydrogenase, succinate cytochrome c reductase, ubiquinone cytochrome c reductase, and cytochrome c oxidase) in EC compared to LDL or control. The abundance of mitochondria-associated ROS and the release of ROS from EC were significantly increased after glyLDL treatment. The findings suggest that glyLDL attenuates the activities of key enzymes in the mitochondrial ETC, decreases mitochondrial oxygen consumption, reduces mitochondrial membrane potential, and increases ROS generation in EC, which potentially contribute to mitochondrial dysfunction in diabetic patients.
Sangle
Ganesh V
GV
Department of Physiology, University of Manitoba, Winnipeg, Canada MB R3E 3P4.
Chowdhury
Subir K Roy
SK
Xie
Xueping
X
Stelmack
Gerald L
GL
Halayko
Andrew J
AJ
Shen
Garry X
GX
D000818:Animals; D001011:Aorta / Q000166:cytology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced; D006861:Hydrogen Peroxide / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D000093844:Glycated Proteins
D017127:Glycation End Products, Advanced; D006861:Hydrogen Peroxide; D008077:Lipoproteins, LDL; D009247:NADH, NADPH Oxidoreductases; D017382:Reactive Oxygen Species; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins