Mitochondrial reactive oxygen species-mediated signaling in endothelial cells

Abstract

Zhang DX, Gutterman DD. Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol 292: H2023-H2031, 2007. First published January 19, 2007; doi:10.1152/ajpheart.01283.2006.-Once thought of as toxic by-products of cellular metabolism, reactive oxygen species (ROS) have been implicated in a large variety of cell-signaling processes. Several enzymatic systems contribute to ROS production in vascular endothelial cells, including NA(D)PH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase, and the mitochondrial electron transport chain. The respiratory chain is the major source of ROS in most mammalian cells, but the role of mitochondriaderived ROS in vascular cell signaling has received little attention. A new paradigm has evolved in recent years postulating that, in addition to producing ATP, mitochondria also play a key role in cell signaling and regulate a variety of cellular functions. This review focuses on the emerging role of mitochondrial ROS as signaling molecules in vascular endothelial cells. Specifically, we discuss some recent findings that indicate that mitochondrial ROS regulate vascular endothelial function, focusing on major sites of ROS production in endothelial mitochondria, factors modulating mitochondrial ROS production, the physiological and clinical implications of endothelial mitochondrial ROS, and methodological considerations in the study of mitochondrial contribution to vascular ROS generation. mitochondria; endothelium REACTIVE OXYGEN SPECIES (ROS), such as superoxide (O 2

Activation of NF-E2–Related Factor-2 Reverses Biochemical Dysfunction of Endothelial Cells Induced by Hyperglycemia Linked to Vascular Disease

“…The lack of similar effect induced by L-glucose indicated that glucose entry and metabolism into cells was required for increased ROS formation. Increased ROS formation was linked to mitochondrial dysfunction, consistent with previous reports (10), in which complexes I and III were involved-the former probably by reverse electron flow from complex II (46). Incubation of HMEC-1 cells with the mitochondrial inhibitors for 24 h produced significant cytotoxicity and masked the role of complex I in hyperglycemia-induced ROS formation.…”

Pinacidil protects osteoblastic cells against antimycin A-induced oxidative damage

“…The transfer of electrons from complex I to V generates a proton concentration gradient across the inner mitochondrial membrane, sustaining the MMP and driving ATP synthesis (34). A failure of efficient electron transport and ATP synthesis induced by oxidative stress results in the accumulation of free radicals and leads to mitochondrial dysfunction (35). In the present study, pre-treatment with pinacidil was found to increase ATP synthesis.…”

The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid

“…In addition to CYP1, several sources of ROS exist, notably the mitochondrial electron transport chain, nicotinamide adenine dinucleotide phosphate-oxidase, and cyclooxygenases. [39][40][41] Note that IAA also has a prooxidant effect in renal tubular cells. 42 Via prooxidant, proinflammatory, and prothrombotic 9 mechanisms, IAA could act as a mediator of endotheliotoxicity of uremia.…”