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PMID:18259862

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Citation

Bhupanapadu Sunkesula, SR, Swain, U and Babu, PP (2008) Cell death is associated with reduced base excision repair during chronic alcohol administration in adult rat brain. Neurochem. Res. 33:1117-28

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.

Links

PubMed Online version:10.1007/s11064-007-9560-1

Keywords

Alcoholism; Animals; Brain/cytology; Brain/metabolism; Brain/pathology; Calpain/metabolism; Caspases/metabolism; Cell Death/physiology; DNA Repair; Enzyme Activation; Ethanol/administration & dosage; Ethanol/metabolism; Humans; In Situ Nick-End Labeling; Male; Protein Subunits/metabolism; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate/metabolism; Subcellular Fractions/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:DPOLB

involved_in

GO:0045471: response to ethanol

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:BCL2

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:BCL2

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:BCL2

involved_in

GO:0045471: response to ethanol

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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