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Putative endogenous mediators of preconditioning‐induced ischemic tolerance in rat brain identified by genomic and proteomic analysis
Author(s) -
Dhodda Vinay K.,
Sailor Kurt A.,
Bowen Kellie K.,
Vemuganti Raghu
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02316.x
Subject(s) - ischemic preconditioning , neuroprotection , heat shock protein , hsp27 , hsp70 , ischemia , biology , brain ischemia , pharmacology , microbiology and biotechnology , neuroscience , medicine , gene , biochemistry
In brain, a brief ischemic episode induces protection against a subsequent severe ischemic insult. This phenomenon is known as preconditioning‐induced neural ischemic tolerance. An understanding of the molecular mechanisms leading to preconditioning helps in identifying potential therapeutic targets for preventing the post‐stroke brain damage. The present study conducted the genomic and proteomic analysis of adult rat brain as a function of time following preconditioning induced by a 10‐min transient middle cerebral artery (MCA) occlusion. GeneChip analysis showed induction of 40 putative neuroprotective transcripts between 3 to 72 h after preconditioning. These included heat‐shock proteins, heme oxygenases, metallothioneins, signal transduction mediators, transcription factors, ion channels and apoptosis/plasticity‐related transcripts. Real‐time PCR confirmed the GeneChip data for the transcripts up‐regulated after preconditioning. Two‐dimensional gel electrophoresis combined with MALDI‐TOF analysis showed increased expression of HSP70, HSP27, HSP90, guanylyl cyclase, muskelin, platelet activating factor receptor and β‐actin at 24 h after preconditioning. HSP70 protein induction after preconditioning was localized in the cortical pyramidal neurons. The infarct volume induced by focal ischemia (1‐h MCA occlusion) was significantly smaller (by 38 ± 7%, p < 0.05) in rats subjected to preconditioning 3 days before the insult. Preconditioning also prevented several gene expression changes induced by focal ischemia.