Bcl-w Expression and Localization in Brain Ischemia

  • R. P. Simon
  • J. Chen
Conference paper


Bcl-w is a newly described cell death-suppressor member of the Bcl-2 gene family. As these genes may have a role in the outcome of ischemic brain injury, the regional expression of Bcl-w protein in rat brain was examined at 6-72 h after 90 min transient middle cerebral artery occlusion. Bcl-w protein, while constitutively expressed at low levels in non-ischemic brain, was found to be overexpressed in ischemic brain at all time points studied. Up regulation of Bcl-w protein was particularly abundant in the penumbral region of the cortex and mainly in cells lacking DNA-fragmentation. In the cortical penumbra, Bcl-w protein was predominantly detected in neurons and showed mitochondrial localization, as determined by double-label immunohistochemistry. Bcl-w expression was also detectable, to a lesser extent, in reactive astrocytes in the infarct border zone and in micro vessel walls in the infarct regions. At the mechanistic level, incubation of isolated brain mitochondria with the addition of recombinant BAX or high concentrations of calcium resulted in release of cytochrome c from the mitochondria. In the presence of recombinant Bcl-w protein, however, the release of cytochrome c induced by BAX or calcium was largely inhibited. Further, recombinant Bcl-w protein inhibited calcium-induced loss of mitochondrial trans membrane potential, indicative of permeability transition, in a dose-dependent manner. These results suggest that Bcl-w is an endogenous neuroprotectant against ischemic neuronal death and that like its analogues such as Bcl-2 and Bcl-xL, Bcl-w may achieve this protection via the mitochondrial death-regulatory pathway.


Ischemic Brain Mitochondrial Transmembrane Potential Penumbral Region Infarct Border Zone Ischemic Neuronal Death 
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  1. 1.
    Chen J, Graham SH, Chan PH, Lan J, Zhou RL, Simon RP (1995) Bcl-w is expressed in neurons that survive focal ischemia in the rat. Neuroreport 6: 394 – 398PubMedCrossRefGoogle Scholar
  2. 2.
    Chen J, Zhu RL, Nakayama M, Kawaguchi K, Jin KL, Stetler RA, Simon RP, Graham SH (1996) Expression of the apoptosis-effector gene, BAX, is up-regulated in vulnerable hippocampal CA1 neurons following global ischemia. J Neurochem 67: 64 – 71PubMedCrossRefGoogle Scholar
  3. 3.
    Chen J, Uchimura K, Stetler RA, Zhu RL, Nakayama M, Jin KL, Graham SH, Simon RP (1998) Transient global ischemia triggers expression of the DNA damage-inducible gene GADD45 in the rat brain. J Cereb Blood Flow Metab 18: 646 – 657PubMedCrossRefGoogle Scholar
  4. 4.
    Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S (1996) Bcl-w, a novel member of the Bcl-w family, promotes cell survival. Oncogene 13: 665 – 675PubMedGoogle Scholar
  5. 5.
    Hammer S, Skoglosa Y, Lindholm D (1999) Differential expression of Bcl-w and Bcl-x messenger RNA in the developing and adult rat nervous system. Neuroscience 91: 673 – 684CrossRefGoogle Scholar
  6. 6.
    Print CG, Loveland KL, Gibson L, Meehan T, Stylianou A, Wreford N, de Kretser D, Metcalf D, Kontgen F, Adams JM, Cory S (1998) Apoptosis regulator Bcl-w is essential for spermatogenesis but appears otherwise redundant. Proc Natl Acad Sci U S A 95: 12424 – 12431PubMedCrossRefGoogle Scholar
  7. 7.
    Reed JC (1998) Bcl-2 family proteins. Oncogene 17: 3255 – 3263CrossRefGoogle Scholar
  8. 8.
    Sadoul R (1998) Bcl-2 family members in the development and degenerative pathologies of the nervous system. Cell Death Differ 5: 805 – 815.PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • R. P. Simon
  • J. Chen

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