心血管系统中AMPK对NAD(P)H氧化酶类的调控

Abstract

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are ubiquitously produced in cardiovascular systems. Under physiological conditions, ROS/RNS function as signaling molecules that are essential in maintaining cardiovascular function. Aberrant concentrations of ROS/RNS have been demonstrated in cardiovascular diseases owing to increased production or decreased scavenging, which have been considered common pathways for the initiation and progression of cardiovascular diseases such as atherosclerosis, hypertension, (re)stenosis, and congestive heart failure. NAD(P)H oxidases are primary sources of ROS and can be induced or activated by all known cardiovascular risk factors. Stresses, hormones, vasoactive agents, and cytokines via different signaling cascades control the expression and activity of these enzymes and of their regulatory subunits. But the molecular mechanisms by which NAD(P)H oxidase is regulated in cardiovascular systems remain poorly characterized. Investigations by us and others suggest that adenosine monophosphate-activated protein kinase (AMPK), as an energy sensor and modulator, is highly sensitive to ROS/RNS. We have also obtained convincing evidence that AMPK is a physiological suppressor of NAD(P)H oxidase in multiple cardiovascular cell systems. In this review, we summarize our current understanding of how AMPK functions as a physiological repressor of NAD(P)H oxidase.

► Adenosine monophosphate-activated protein kinase (AMPK) is activated by oxidants. ► AMPK suppresses NAD(P)H oxidase. ► Dysfunctional AMPK results in oxidative stress.
Abbreviations
• 7-KC, 7-ketocholesterol;
• AAA, abdominal aortic aneurysm;
• AICAR, 5′-aminoimidazole-4-carboxamide ribonucleoside;
• AMPK, adenosine monophosphate-activated protein kinase;
• AngII, angiotensin II;
• ApoE, apolipoprotein E;
• BH4, 5,6,7,8-tetrahydrobiopterin;
• CaMKKβ, Ca2+/calmodulin-dependent protein kinase kinase β;
• CVD, cardiovascular disease;
• EC, endothelial cell;
• EGF, epidermal growth factor;
• eNOS, endothelial nitric oxide synthase;
• ER, endoplasmic reticulum;
• ET-1, endothelin 1;
• GTPCH1, GTP-cyclohydrolase 1;
• HUVEC, human umbilical vein endothelial cell;
• LKB1, liver kinase B1;
• NAD(P)H, nicotinamide adenine dinucleotide phosphate reduced form;
• NF-κB, nuclear factor κB;
• Nox, NAD(P)H oxidase;
• O2•−, superoxide anion;
• ONOO−, peroxynitrite;
• PC, preconditioning;
• PDGF, platelet-derived growth factor;
• PDI, protein disulfide isomerase;
• PGC-1α, peroxisome proliferator-activated response-γ coactivator-1α;
• PKA, protein kinase A;
• PKC, protein kinase C;
• PM, plasma membrane;
• RNS, reactive nitrogen species;
• ROS, reactive oxygen species;
• SERCA, sarcoplasmic/endoplasmic reticulum Ca2+ ATPase;
• SOD, superoxide dismutase;
• TAC, transverse aortic constriction;
• TAK1, transforming growth factor-β-activated kinase 1;
• TGFβ1, transforming growth factor β1;
• TNFα, tumor necrosis factor α;
• TP, thromboxane A2 receptor;
• TZD, thiazolidinedione;
• SMC, smooth muscle cell;
• VSMC, vascular smooth muscle cell;
• WT, wild type
Keywords
• NAD(P)H oxidase;
• Endothelial cells;
• Vascular smooth muscle cells;
• Blood cells;
• AMPK;
• Cardiovascular diseases;
• Free radicals