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Puma is a critical regulator of acute ethanol‐induced neuroapoptosis
Author(s) -
Ghosh Arindam,
Klocke Barbara J,
Roth Kevin Aaron
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.926.8
Subject(s) - puma , apoptosis , neurodegeneration , regulator , synaptogenesis , knockout mouse , biology , endocrinology , medicine , microbiology and biotechnology , chemistry , neuroscience , gene , biochemistry , disease
Intrauterine exposure to ethanol causes a dysmorphogenic neuropathological syndrome in humans. The toxic effects are most pronounced during the synaptogenesis period of nervous system development that predominantly occurs prenatally in humans but postnatally in rodents. To define the critical upstream pro‐apoptotic mediators of acute ethanol‐induced neuroapoptosis, we examined the effects of ethanol administration in wild type mice and mice with targeted gene disruptions in puma, bax, noxa and p53.Apoptosis as evidenced by a robust increase in cleaved caspase‐3 like immunoreactivity was observed at 6 hours post treatment. Bax deficient mice however did not show an increase in cleaved caspase‐3 levels indicating that Bax deficiency is protective in this process. Puma knockout mice also did not show an elevation in cleaved caspase‐3 levels after treatment with ethanol, though p53 deficient animals treated with ethanol showed comparable caspase‐3 levels as p53 heterozygous mice or wild type mice. These results indicate that acute ethanol‐induced neurodegeneration is mediated by Puma and Bax and is independent of regulation by p53.The transcription factor that mediates this process remains to be determined. This work was supported by UAB Neuroscience Core facilities (NS 47466 and NS57098) and NIH grant NS35107 (KAR)