Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia

被引：29

作者：

Abe, T ^{[1
]}

Takagi, N ^{[1
]}

Nakano, M ^{[1
]}

Furuya, M ^{[1
]}

Takeo, S ^{[1
]}

机构：

[1] Tokyo Univ Pharm & Life Sci, Dept Pharmacol, Fac Pharmaceut Sci, Hachioji, Tokyo 1910392, Japan

来源：

BRAIN RESEARCH | 2004年 / 1009卷 / 1-2期

关键词：

Bad; Bcl-xL; mitochondria; transient global ischemia;

D O I：

10.1016/j.brainres.2004.03.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Accumulating evidence indicates that the mitochondrial cell-death pathway, which involves the release of cytochrome c from mitochondria, participates in neuronal cell death after transient cerebral ischemia. However, the upstream events, that induce cytochrome c release after transient global ischemia are not fully understood. Bad is a pro-apoptotic member of the bcl-2 gene family that promotes apoptosis by binding to and inhibiting functions of anti-apoptotic proteins Bcl-2 and Bcl-xL. We investigated the effects of transient (15 min) global ischemia on the intracellular localization of Bad and the interaction of Bad with calcineurin, Akt or Bcl-xL in the vulnerable CA1 and resistant CA3/dentate gyrus of the hippocampus. Immunoblotting analysis revealed that the amount of Bad in mitochondria significantly increased after ischemia. Co-immunoprecipitation studies showed decreased interactions of Bad with Akt and calcineurin in the cytosol and increased binding with Bcl-xL in the mitochondrial fraction of hippocampal CA1, but not in the CA3/dentate gyros region. Further, we examined the effect of recombinant Bad on the cytochrome c release front isolated mitochondria. Treatment with both recombinant Bad and calcium, but not with recombinant Bad alone, induced cytochrome c release. These results suggest that changes in localization and complex formation by Bad are, at least in part, involved in the vulnerability of cells after transient global ischemia. (C) 2004 Elsevier B.V. All rights reserved.

引用

页码：159 / 168

页数：10

共 50 条

[31]

Polster BM, 2003, J NEUROSCI, V23, P2735

[32]

Saito A, 2003, J NEUROSCI, V23, P1710

[33] Regulation of bad phosphorylation and association with Bcl-xL by the MAPK/Erk kinase [J].

Scheid, MP ;

Schubert, KM ;

Duronio, V .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (43) :31108-31113

[34] RAPID ISOLATION OF METABOLICALLY ACTIVE MITOCHONDRIA FROM RAT-BRAIN AND SUBREGIONS USING PERCOLL DENSITY GRADIENT CENTRIFUGATION [J].

SIMS, NR .

JOURNAL OF NEUROCHEMISTRY, 1990, 55 (02) :698-707

[35] Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury [J].

Springer J.E. ;

Azbill R.D. ;

Knapp P.E. .

Nature Medicine, 1999, 5 (8) :943-946

[36]

Springer JE, 2000, J NEUROSCI, V20, P7246

[37] A MODEL OF BILATERAL HEMISPHERIC ISCHEMIA - MODIFIED 4-VESSEL OCCLUSION IN RATS [J].

SUGIO, K ;

HORIGOME, N ;

SAKAGUCHI, T ;

GOTO, M .

STROKE, 1988, 19 (07) :922-922

[38] Transient ischemia enhances tyrosine phosphorylation and binding of the NMDA receptor to the Src homology 2 domain of phosphatidylinositol 3-kinase in the rat hippocampus [J].

Takagi, N ;

Sasakawa, K ;

Besshoh, S ;

Miyake-Takagi, K ;

Takeo, S .

JOURNAL OF NEUROCHEMISTRY, 2003, 84 (01) :67-76

[39] p90RSK blocks bad-mediated cell death via a protein kinase C-dependent pathway [J].

Tan, Y ;

Ruan, H ;

Demeter, MR ;

Comb, MJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (49) :34859-34867

[40] Differential neuroprotection by cyclosporin A and FK506 following ischemia corresponds with differing abilities to inhibit calcineurin and the mitochondrial permeability transition [J].

Uchino, H ;

Minamikawa-Tachino, R ;

Kristián, T ;

Perkins, G ;

Narazaki, M ;

Siesjö, BK ;

Shibasaki, F .

NEUROBIOLOGY OF DISEASE, 2002, 10 (03) :219-233

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