A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

Y. Sari, T. Chiba, M. Yamada, G. V. Rebec, S. Aiso

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet 25% (4.49% v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ethanol liquid diet combined with administration (i.p.) of CLN (20 μg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 μg/20 g body weight). On E13, fetal brains were collected and assayed for TdT-mediated dUTP nick end labeling staining, caspase-3 colorimetric assay, enzyme-linked immunosorbent assay, and Meso scale discovery electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies.

Original languageEnglish
Pages (from-to)1653-1664
Number of pages12
JournalNeuroscience
Volume164
Issue number4
DOIs
Publication statusPublished - 2009 Dec 29

Keywords

  • ADNF-9
  • caspase-3
  • colivelin
  • cytochrome c
  • mitochondria
  • neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

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