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Dynamic changes of the anti- and pro-apoptotic proteins Bcl-w, Bcl-2, and Bax with Smac/Diablo mitochondrial release after photothrombotic ring stroke in rats

Hu, Xiao-Lei (author)
Umeå universitet,Medicin
Olsson, Tommy (author)
Umeå universitet,Medicin
Johansson, Inga-Maj (author)
Umeå universitet,Obstetrik och gynekologi,Medicin
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Brännström, Thomas (author)
Umeå universitet,Patologi,Umeå Stroke Centre, Umeå University Hospita
Wester, Per (author)
Umeå universitet,Medicin
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 (creator_code:org_t)
Wiley-Blackwell, 2004
2004
English.
In: European Journal of Neuroscience. - : Wiley-Blackwell. - 0953-816X .- 1460-9568. ; 20:5, s. 1177-1188
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The anti‐apoptotic proteins Bcl‐w and Bcl‐2 and the pro‐apoptotic protein Bax may mediate cell death or survival via regulation of the mitochondria including second mitochondria‐derived activator of caspase (Smac)/direct inhibitor of apoptosis protein (IAP)‐binding protein with low pI (DIABLO) release. This study aimed to explore alterations in Bcl‐w, Bcl‐2, and Bax and the relationship between these proteins and Smac/DIABLO by means of in situ hybridization, immunohistochemical (IHC) staining, and Western blots after low‐ and high‐intensity photothrombotic ring stroke. At 4 h after low‐intensity irradiation, we found widespread bcl‐w overexpression on both the mRNA and protein levels in the bilateral cortex except the ring lesion region and in subcortical regions. A prolonged elevation of Bcl‐2 with relatively unchanged Bax in the mitochondrial fraction was demonstrated from 4 to 72 h. These upregulated anti‐apoptotic proteins combined with little Smac/DIABLO release might be associated with increased cell survival and thereby remarkable morphological recovery after low‐intensity irradiation. After high‐intensity irradiation, we observed decreased bcl‐w and bcl‐2 mRNA with increased Bcl‐2 protein in the cytosolic fraction, whereas the Bax protein remained in scattered ischaemic cells in the ring lesion and the region at risk that corresponded with release of Smac/DIABLO from mitochondria to the cytosol at 1–24 h. These changes might be related to the massive cell death observed after high‐intensity irradiation. Taken together, the balance and the location of anti‐apoptotic proteins vs. pro‐apoptotic proteins could be associated with the translocation of Smac/DIABLO from the mitochondria to the cytosol and therefore closely related to cell death or survival after focal cerebral ischaemia.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Animals
Apoptosis/*physiology
Apoptosis Regulatory Proteins
Brain/metabolism
Carrier Proteins/analysis/*biosynthesis
Cell Survival/physiology
Cerebrovascular Accident/*metabolism
Intracranial Thrombosis/metabolism
Mitochondrial Proteins/analysis/*biosynthesis
Protein Biosynthesis
Proteins/analysis
Proto-Oncogene Proteins c-bcl-2/analysis/*biosynthesis
RNA; Messenger/analysis/biosynthesis
Rats
bcl-2-Associated X Protein

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ref (subject category)
art (subject category)

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By the author/editor
Hu, Xiao-Lei
Olsson, Tommy
Johansson, Inga- ...
Brännström, Thom ...
Wester, Per
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Neurosciences
Articles in the publication
European Journal ...
By the university
Umeå University

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