Cell Death is Associated with Reduced Base Excision Repair During Chronic Alcohol Administration in Adult Rat Brain |
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Authors: | Solomon?Raju?Bhupanapadu Sunkesula Umakanta?Swain Email author" target="_blank">Phanithi?Prakash?BabuEmail author |
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Institution: | (1) Centre for Biotechnology and Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India;(2) Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India |
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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. |
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Keywords: | Chronic alcoholism Apoptosis Necrosis DNA-repair |
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