Vascular NAD(P)H oxidases: specific features, expression, and regulation
Tóm tắt
The importance of reactive oxygen species (ROS) in vascular physiology and pathology is becoming increasingly evident. All cell types in the vascular wall produce ROS derived from superoxide-generating protein complexes similar to the leukocyte NADPH oxidase. Specific features of the vascular enzymes include constitutive and inducible activities, substrate specificity, and intracellular superoxide production. Most phagocyte enzyme subunits are found in vascular cells, including the catalytic gp91phox (aka, nox2), which was the earliest member of the newly discovered nox family. However, smooth muscle frequently expresses nox1 rather than gp91phox, and nox4 is additionally present in all cell types. In cell culture, agonists increase ROS production by activating multiple signals, including protein kinase C and Rac, and by upregulating oxidase subunits. The oxidases are also upregulated in vascular disease and are involved in the development of atherosclerosis and a significant part of angiotensin II-induced hypertension, possibly via nox1 and nox4. Likewise, enhanced vascular oxidase activity is associated with diabetes. Therefore, members of this enzyme family appear to be important in vascular biology and disease and constitute promising targets for future therapeutic interventions.
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Dikalov S, Fink B, Skatchkov M, Stalleicken D, and Bassenge E.Formation of reactive oxygen species by pentaerithrityltetranitrate and glyceryl trinitrate in vitro and development of nitrate tolerance.J Pharmacol Exp Ther286: 938–944, 1998.
Hanna IR, Dikalova AE, Hilenski LL, Quinn MT, and Griendling KK.Nox1 binds p22phox to form a functional oxidase in vascular smooth muscle cells (VSMCs) (Abstract).Circulation106: SII-164, 2002.
Harrison DG, Galis Z, Parthasarathy S, and Griendling KK.Oxidative stress and hypertension. In:Hypertension Primer(2nd ed.), edited by Izzo JL Jr and Black HR. Baltimore: Lippincott, Williams and Wilkins, 1999, p. 163–166.
Heinloth A, Heermeier K, Raff U, Wanner C, and Galle J.Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces proliferation of human vascular endothelial cells.J Am Soc Nephrol11: 1819–1825, 2000.
Hilenski LL, Clempus RE, and Griendling KK.NAD(P)H oxidase subunits nox1 and nox4 are differentially localized in the membrane and in focal adhesions in vascular smooth muscle cells (Abstract).Circulation106: SII-283, 2002.
Hohler B, Holzapfel B, and Kummer W.NADPH oxidase subunits and superoxide production in porcine pulmonary artery endothelial cells.Histochem Cell Biol114: 29–37, 2000.
Lynch REand Fridovich I.Permeation of the erythrocyte stroma by superoxide radical.J Biol Chem253: 4697–4699, 1978.
Matsushita H, Lee KH, and Tsao PS.Cyclic strain induces reactive oxygen species production via an endothelial NAD(P)H oxidase.J Cell BiochemS-36: 99–106, 2001.
Parthasarathy S, Santanam N, Ramachandran S, and Meilhac O.Oxidants and antioxidants in atherogenesis: an appraisal.J Lipid Res40: 2143–2157, 1999.
Touyz RMand Schiffrin EL.Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells.Pharmacol Rev52: 639–672, 2000.
Wyche KE, Griendling KK, Dikalov SI, Austin H, Sorescu D, Harrison DG, and Zafari AM.The C242T p22phox polymorphism of the NADPH oxidase is associated with reduced superoxide production in human neutrophils (Abstract).Circulation104: SII-40, 2001.
Yokoyama M, Inoue N, and Kawashima S.Role of the vascular NADH/NADPH oxidase system in atherosclerosis.Ann NY Acad Sci902: 241–248, 2000.
Zafari AM, Harrison DG, and Griendling KK.Vascular oxidant stress and nitric oxide bioactivity. In:Endothelium, Nitric Oxide, and Atherosclerosis, edited by Panza JA and Cannon RO III. Armonk, NY: Futura, 1999, p. 133–144.
Zalba G, Beaumont FJ, San Jose G, Fortuno A, Fortuno MA, and Diez J.Is the balance between nitric oxide and superoxide altered in spontaneously hypertensive rats with endothelial dysfunction?Nephrol Dial Transplant16: 2–5, 2001.