Effects of ethanol-induced p42/44 MAPkinase activity on IGF system in primary cultured rat hepatocytes

흰쥐의 배양된 간세포에서 ethanol에 의해 유도된 p42/44 MAPkinase가 IGF system에 미치는 효과

  • Lee, Sun-Mi (College of Veterinary Medicine, Bio-safety Research Institute, Chonbuk National University) ;
  • Kim, Jong-Hoon (College of Veterinary Medicine, Bio-safety Research Institute, Chonbuk National University) ;
  • Kang, Chang-Won (College of Veterinary Medicine, Bio-safety Research Institute, Chonbuk National University)
  • 이선미 (전북대학교 수의과대학, 생체안전성 연구소) ;
  • 김종훈 (전북대학교 수의과대학, 생체안전성 연구소) ;
  • 강창원 (전북대학교 수의과대학, 생체안전성 연구소)
  • Accepted : 2006.12.03
  • Published : 2006.12.30

Abstract

Ethanol abuse is associated with liver injury, neurotoxicity, modulation of immune responses, and increased risk for cancer, whereas moderate ethanol consumption exerts protective effects against liver injury. However, the underlying signal transduction mechanisms of insulin-like growth factors (IGFs) which play an important regulatory role in various metabolism mechanisms are not well understood. We investigated the effects of ethanol-induced p42/44 activity on IGF-I secretion, IGF-I receptor and IGFBP-1 secretion using radioimmunoassay and western blotting in primary cultured rat hepatocytes. The p42/44 activity, IGF-I secretion and IGF-I receptor activity significantly accelerated compared to control at 10 and 30 min after 200 mM ethanol treatment, but then it became suppressed at 180 min. In contrast, IGFBP-1 secretion was inhibited compared to control at 30 min after 200 mM ethanol treatment, but increased at 180 min. The IGF-I secretion, IGF-I receptor and p42/44 activity at 30 min after 200 mM ethanol treatment accelerated with increasing ethanol concentration but IGFBP-1 secretion inhibited (p<0.05). The increased IGF-I secretion, inhibited IGFBP-1 secretion and IGF-IR activity by ethanol-induced temporal p42/44 activity at 30 min after ethanol treatment was blocked by treatment with PD98059. Alcohol dehydrogenase (ADH) inhibitor, 4-methylpyramazole blocked the changes of IGF-I secretion, IGFBP-1 secretion, and IGF-IR activity by ethanol-induced p42/44 activity at 30 and 180 min. Taken together, these results suggest that ethanol is involved in the modulation of IGF-I and IGFBP-1 secretion and IGF-IR activity by p42/44 activity in primary cultured rat hepatocytes. In addition, changing of p42/44 activity by ethanol was caused with ADH.

Acknowledgement

Supported by : 전북대학교

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