LOSS OF AUTOPHAGY ENHANCES DIETHYLNITROSAMINE-INDUCED LIVER INJURY

  • ABUDOXUEKE MIHEGULI
    DEPARTMENT OF GASTROENTEROLOGY, JUNTENDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE
  • YAMASHINA SHUNHEI
    DEPARTMENT OF GASTROENTEROLOGY, JUNTENDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE
  • IKEJIMA KENICHI
    DEPARTMENT OF GASTROENTEROLOGY, JUNTENDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE
  • KOMATSU MASAAKI
    THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
  • TANAKA KEIJI
    THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
  • WATANABE SUMIO
    DEPARTMENT OF GASTROENTEROLOGY, JUNTENDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE

Bibliographic Information

Other Title
  • ジエチルニトロソアミン投与後肝障害におけるオートファジーの関与について
  • ジエチルニトロソアミン トウヨ ゴ カン ショウガイ ニ オケル オートファジー ノ カンヨ ニ ツイテ

Search this article

Abstract

Objective : Previous reports indicated that mitochondrial dysfunction is essential for the development of liver injury due to diethylnitrosamine (DEN). On the other hand, autophagy, which is a major catabolic pathway, plays a critical role in removing protein aggregates, as well as damaged or excess mitochondria in order to maintain intracellular homeostasis. The aim of this study was to clarify if autophagy is linked to liver injury due to DEN. Methods : DEN was administered intraperitoneally (10mg/kg) to male C57BL/6mice (wild type) and conditional Atg7-knockout mice, which have autophagy-deficient livers. Mice of both genotypes were sacrificed 24 and 48 hours after administration of DEN. Liver tissues embedded in paraffin were cut and stained with H&E. TUNEL-staining was performed to evaluate apoptotic cells. Serum ALT value was measured to evaluate liver damage. Moreover, expression of caspase-3 and 7 were detected by Western blot analysis. Results : Serum ALT levels before administration of DEN were not significantly different between wild-type mice and conditional Atg7-knockout mice. Serum ALT levels at 48 hours after administration of DEN were elevated to about 7-fold in conditional Atg7-knockout mice but not control mice. Autophagy deficiency enhanced the number of TUNEL-positive cells and activation of caspase-3 and 7 in the liver after administration of DEN. Conclusions : Our data indicates that loss of autophagy enhances apoptosis of hepatocytes and liver injury due to DEN. These findings suggest that autophagy plays a pivotal role to prevent the excessive cell death of hepatocyte in DEN-induced liver injury.

Journal

References(45)*help

See more

Details 詳細情報について

Report a problem

Back to top