The mitochondrial KATP channel opener BMS-191095 induces neuronal preconditioning

被引：60

作者：

Kis, B

Nagy, K

Snipes, JA

Rajapakse, NC

Horiguchi, T

Grover, GJ

Busija, DW

机构：

[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA

[2] Univ Szeged, Sch Med, Dept Physiol, Szeged, Hungary

[3] Bristol Myers Squibb Pharmaceut Res Inst, Pennington, NJ USA

来源：

NEUROREPORT | 2004年 / 15卷 / 02期

关键词：

BMS-191095; free radicals; glutamate; MitcoK(ATP) channel; oxygen-glucose deprivation; preconditioning; protein kinase C;

D O I：

10.1097/00001756-200402090-00027

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

BMS-191095, reportedly a selective mitoK(ATP) channel opener which is free from the known side effects of the prototype mitoK(ATP) channel opener diazoxide, induced acute and delayed preconditioning against glutamate excitotoxicity and delayed preconditioning against oxygen-glucose deprivation in primary cultures of rat cortical neurons. BMS-191095 dose dependently depolarized the mitochondria, increased the phosphorylation of PKC isoforms, but had no detectable effects on the activation of MAP kinases and did not influence the expressions of HSP70 and Mn-SOD. In BMS-191095-preconditioned neurons the glutamate-induced free-radical production was abolished. Our data give the first evidence that selective opening of mitoK(ATP) channels with BMS-191095 leads to remarkable neuroprotection via mechanisms that involve mitochondrial depolarization, PKC activation and attenuated free radical production during neuronal stress.

引用

收藏

页码：345 / 349

页数：5

相关论文

共 20 条

[11] Investigation of the subunit composition and the pharmacology of the mitochondrial ATP-dependent K+ channel in the brain [J].

Lacza, Z ;

Snipes, JA ;

Kis, B ;

Szabó, C ;

Grover, G ;

Busija, DW .

BRAIN RESEARCH, 2003, 994 (01) :27-36

[12] The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration [J].

Lim, KHH ;

Javadov, SA ;

Das, M ;

Clarke, SJ ;

Suleiman, MS ;

Halestrap, AP .

JOURNAL OF PHYSIOLOGY-LONDON, 2002, 545 (03) :961-974

[13] Involvement of mitochondrial K+ release and cellular efflux in ischemic and apoptotic neuronal death [J].

Liu, D ;

Slevin, JR ;

Lu, CB ;

Chan, SL ;

Hansson, M ;

Elmér, E ;

Mattson, MP .

JOURNAL OF NEUROCHEMISTRY, 2003, 86 (04) :966-979

[14] Activation of mitochondrial, ATP-dependent potassium channels protects neurons against ischemia-induced death by a mechanism involving suppression of bax translocation and cytochrome c release [J].

Liu, D ;

Lu, CB ;

Wan, RQ ;

Auyeung, WW ;

Mattson, MP .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2002, 22 (04) :431-443

[15] Potassium channel openers protect cardiac mitochondria by attenuating oxidant stress at reoxygenation [J].

Ozcan, C ;

Bienengraeber, M ;

Dzeja, PP ;

Terzic, A .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 282 (02) :H531-H539

[16] Diazoxide pretreatment induces delayed preconditioning in astrocytes against oxygen glucose deprivation and hydrogen peroxide-induced toxicity [J].

Rajapakse, N ;

Kis, B ;

Horiguchi, T ;

Snipes, J ;

Busija, D .

JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 73 (02) :206-214

[17] Activation of mitochondrial ATP-sensitive potassium channels prevents neuronal cell death after ischemia in neonatal rats [J].

Rajapakse, N ;

Shimizu, K ;

Kis, B ;

Snipes, J ;

Lacza, Z ;

Busija, D .

NEUROSCIENCE LETTERS, 2002, 327 (03) :208-212

[18] MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat [J].

Shimizu, K ;

Lacza, Z ;

Rajapakse, N ;

Horiguchi, T ;

Snipes, J ;

Busija, DW .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 283 (03) :H1005-H1011

[19] Protective effect of a new nonpeptidyl mimetic of SOD, M40401, against focal cerebral ischemia in the rat [J].

Shimizu, K ;

Rajapakse, N ;

Horiguchi, T ;

Payne, RM ;

Busija, DW .

BRAIN RESEARCH, 2003, 963 (1-2) :8-14

[20] HUMAN COPPER-ZINC SUPEROXIDE-DISMUTASE TRANSGENIC MICE ARE HIGHLY RESISTANT TO REPERFUSION INJURY AFTER FOCAL CEREBRAL-ISCHEMIA [J].

YANG, GY ;

CHAN, PH ;

CHEN, J ;

CARLSON, E ;

CHEN, SF ;

EPSTEIN, P ;

KAMII, H .

STROKE, 1994, 25 (01) :165-170