Provoking neuroprotection by peroxynitrite

被引:40
作者
Bolaños, JP
García-Nogales, P
Almeida, A
机构
[1] Univ Salamanca, Dept Bioquim & Biol Mol, Edif Dept, E-37007 Salamanca, Spain
[2] Hosp Univ Salamanca, Unidad Invest, Salamanca, Spain
关键词
peroxynitrite; nitric oxide; neuroprotection; glutathione; tyrosine kinase receptor; PI-3-K; Akt;
D O I
10.2174/1381612043452910
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Peroxynitrite, the product of the reaction between nitric oxide and superoxide, is spontaneouly formed within most mammalian cells under physiological conditions. Initial work addressing the pathophysiology of peroxynitrite afforded the generally accepted notion that this compound would be the long-term neurotoxic nitric oxide-derivative. However, over the past six years a number of interesting studies have reported direct in vivo and in vitro evidence that, at nanomolar-low micromolar concentrations, peroxynitrite is actively involved in triggering cellular survival signals. Most such evidence came from studies demonstrating protection against myocardial ischemia-reperfusion injury and neuronal apoptosis. Although full elucidation of the precise mechanism responsible for such protection still requires further research, peroxynitrite has been shown to promote the nitration and/or phosphorylation of regulatory sites at tyrosine kinase receptors coupled to well-known antiapoptotic pathways, such as those involving phosphoinositide 3-kinase/Akt or mitogen-activated protein kinases. In addition, peroxynitrite-mediated transient protection of neurons against apoptotic death is associated with rapid stimulation of glucose metabolism and glutathione regeneration. In view of the potential cytoprotective function of peroxynitrite, further studies specifically focused on elucidating the possible therapeutic potential of peroxynitrite are sure to appear.
引用
收藏
页码:867 / 877
页数:11
相关论文
共 155 条
[1]   The ferrous-dioxy complex of neuronal nitric oxide synthase - Divergent effects of L-arginine and tetrahydrobiopterin on its stability [J].
AbuSoud, HM ;
Gachhui, R ;
Raushel, FM ;
Stuehr, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (28) :17349-17353
[2]   DIFFERENT RECEPTORS MEDIATE STIMULATION OF NITRIC OXIDE-DEPENDENT CYCLIC-GMP FORMATION IN NEURONS AND ASTROCYTES IN CULTURE [J].
AGULLO, L ;
GARCIA, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 182 (03) :1362-1368
[3]   CHARACTERIZATION OF NORADRENALINE-STIMULATED CYCLIC-GMP FORMATION IN BRAIN ASTROCYTES IN CULTURE [J].
AGULLO, L ;
GARCIA, A .
BIOCHEMICAL JOURNAL, 1992, 288 :619-624
[4]   The beneficial effects of peroxynitrite on ischaemia-reperfusion arrhythmias in rat isolated hearts [J].
Altug, S ;
Demiryürek, AT ;
Çakici, I ;
Kanzuk, I .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 384 (2-3) :157-162
[5]   GLUTAMATE-INDUCED NEURONAL DEATH - A SUCCESSION OF NECROSIS OR APOPTOSIS DEPENDING ON MITOCHONDRIAL-FUNCTION [J].
ANKARCRONA, M ;
DYPBUKT, JM ;
BONFOCO, E ;
ZHIVOTOVSKY, B ;
ORRENIUS, S ;
LIPTON, SA ;
NICOTERA, P .
NEURON, 1995, 15 (04) :961-973
[6]   Trypanothione as a target in the design of antitrypanosomal and antileishmanial agents [J].
Augustyns, K ;
Amssoms, K ;
Yamani, A ;
Rajan, PK ;
Haemers, A .
CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (12) :1117-1141
[7]   Glutathione protects astrocytes from peroxynitrite-mediated mitochondrial damage: Implications for neuronal astrocytic trafficking and neurodegeneration [J].
Barker, JE ;
Bolanos, JP ;
Land, JM ;
Clark, JB ;
Heales, SJR .
DEVELOPMENTAL NEUROSCIENCE, 1996, 18 (5-6) :391-396
[8]   Oxidatively modified proteins in aging and disease [J].
Beal, MF .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (09) :797-803
[9]   Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis [J].
Beal, MF ;
Ferrante, RJ ;
Browne, SE ;
Matthews, RT ;
Kowall, NW ;
Brown, RH .
ANNALS OF NEUROLOGY, 1997, 42 (04) :644-654
[10]   APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE [J].
BECKMAN, JS ;
BECKMAN, TW ;
CHEN, J ;
MARSHALL, PA ;
FREEMAN, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) :1620-1624