Effectors of alcohol-induced cell killing in Drosophila

Chen P., Tu X., Akdemir F., Chew S. K., Rothenfluh A., Abrams J. M.

CELL DEATH AND DIFFERENTIATION, cilt.19, sa.10, ss.1655-1663, 2012 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19 Sayı: 10
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1038/cdd.2012.47
  • Dergi Adı: CELL DEATH AND DIFFERENTIATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1655-1663
  • Anahtar Kelimeler: alcohol, apoptosis, Drosophila, HEPATOCYTE APOPTOSIS, DEATH PATHWAY, LIVER-INJURY, ETHANOL, FIBROSIS, STRESS, KINASE, ASSAYS, BRAIN, MICE
  • Atatürk Üniversitesi Adresli: Evet

Özet

Heavy alcohol consumption provokes an array of degenerative pathologies but the signals that couple alcohol exposure to regulated forms of cell death are poorly understood. Using Drosophila as a model, we genetically establish that the severity of ethanol challenge dictates the type of death that occurs. In contrast to responses seen under acute exposure, cytotoxic responses to milder challenges required gene encoding components of the apoptosome, Dronc and Dark. We conducted a genome-wide RNAi screen to capture targets that specifically mediate ethanol-induced cell death. One effector, Drat, encodes a novel protein that contains an ADH domain but lacks essential residues in the catalytic site. In cultured cells and neurons in vivo, depletion of Drat conferred protection from alcohol-induced apoptosis. Adults mutated for Drat showed both improved survival and enhanced propensities toward sedation after alcohol challenge. Together, these findings highlight novel effectors that support regulated cell death incited by alcohol stress in vitro and in vivo. Cell Death and Differentiation (2012) 19, 1655-1663; doi:10.1038/cdd.2012.47; published online 27 April 2012