title: Cell death is associated with reduced base excision repair during chronic alcohol administration in adult rat brain.
abstract: The cell death cascades in different brain regions namely hippocampus and frontal cortex of rats fed with 10% (v/v) ethanol for 12 weeks, was examined. After Western blotting, different cell death associated proteins displayed differential activation in the two regions observed. In hippocampus, activated caspase-3 and caspase-7 resulted in subsequent cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). Cytochrome c release to cytosol and apoptosis inducing factor (AIF) translocation to nucleus was marginal. B-cell leukemia/lymphoma-2 (Bcl-2) translocation to cytosol was significant whereas Bcl-2-associated X protein (Bax) and Bcl-associated death protein (Bad) were largely located in cytosol. Further, upregulation of N-methyl D-aspartate receptor subunit 1 (NMDAR1), N-methyl D-aspartate receptor subunit 2B (NMDAR2B), N-methyl D-aspartate receptor subunit 2C (NMDAR2C) and activation of calpains were observed. In frontal cortex, caspase-3 activation, cleavage of PARP-1 and nuclear translocation of AIF were more pronounced. Moreover, cytochrome c release to cytosol, Bcl-2 translocation to cytosol was evident. However, levels of Bax, Bad, NMDA receptor subunits, and calpains were unaffected. Apoptosis was further substantiated by in situ staining for terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). Results of the current study revealed that frontal cortex exhibits a higher level of ethanol-induced apoptosis relative to hippocampus. DNA polymerase beta assay and immunoblot showed significant loss in base excision repair in ethanol treated group.
authors.affiliation: Centre for Biotechnology and Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Solomon Raju
authors.initials: SR
authors.lastname: Bhupanapadu Sunkesula
authors.forename: Umakanta
authors.initials: U
authors.lastname: Swain
authors.forename: Phanithi Prakash
authors.initials: PP
authors.lastname: Babu
mesh_terms: D000437:Alcoholism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D004260:DNA Repair; D004789:Enzyme Activation; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry
chemical_list: D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D002154:Calpain; D020169:Caspases