Document Detail


Multiple apoptogenic proteins are involved in the nuclear translocation of Apoptosis Inducing Factor during transient focal cerebral ischemia in rat.
MedLine Citation:
PMID:  18938146     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis Inducing Factor is a mitochondrial protein which upon translocation to nucleus causes large scale DNA fragmentation. The stimulus for the cytosolic release and nuclear translocation for this protein still remains to be understood. The role of calpains, cathepsin-b, Poly ADP (ribose) Polymerase and granzyme-b in the nuclear translocation of AIF has been investigated in the pathology of cerebral ischemia. Calpains, cathepsin-b and PARP-1 which were mostly confined to cytosol, lysosomes and nucleus respectively were found to be elevated in the mitochondrial fraction interacting with AIF in the western blot analysis and double immunofluorescence analysis. Western blot and immunohistochemical analysis revealed elevated levels of granzyme-b secreted by cytotoxic T lymphocytes and natural killer cells in the infarct of ischemic mouse brain. Co-immunoprecipitation revealed and western blot analysis the interaction and break down of Heat Shock Protein-70 an endogenous inhibitor of AIF into signature fragments by granzyme-b facilitating the nuclear translocation of AIF. Break down of HSP-70 correlated with the nuclear translocation of AIF observed in western and immunohistochemical analysis. These results indicate that multiple proteases were involved in the nuclear translocation of AIF during the pathology of cerebral ischemia.
Authors:
Ganta Vijay Chaitanya; Phanithi Prakash Babu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-09
Journal Detail:
Title:  Brain research     Volume:  1246     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-01-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  178-90     Citation Subset:  IM    
Affiliation:
Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad-50046, India.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Animals
Apoptosis Inducing Factor / metabolism*
Blotting, Western
Brain / metabolism*
Calpain / metabolism
Cathepsin B / metabolism
Cell Nucleus / metabolism*
Fluorescent Antibody Technique
Granzymes / metabolism,  secretion
HSP70 Heat-Shock Proteins / metabolism
Immunoprecipitation
Infarction, Middle Cerebral Artery / pathology,  physiopathology
Ischemic Attack, Transient / metabolism*,  pathology
Male
Mice
Mitochondria / metabolism
Neurons / metabolism,  pathology
Poly(ADP-ribose) Polymerases / metabolism*
Random Allocation
Rats
T-Lymphocytes, Cytotoxic / physiology
Chemical
Reg. No./Substance:
0/Apoptosis Inducing Factor; 0/HSP70 Heat-Shock Proteins; EC 2.4.2.30/Adprt protein, rat; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.21.-/Granzymes; EC 3.4.22.-/Calpain; EC 3.4.22.1/Cathepsin B

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