Electric Foot Shock Stress-Induced Exacerbation of α -Galactosylceramide-Triggered Apoptosis in Mouse Liver

Yoichi Chida, Nobuyuki Sudo, Junko Sonoda, Hiroshi Sogawa, Chiharu Kubo

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Recently, liver natural killer T (NKT) cells, which are specifically stimulated by α-galactosyl-ceramide (α-GalCer), were found to play a critical role in intrahepatic immunity to several infections and certain hepatic disorders. However, the role of psychophysical stress on NKT cell-dependent liver injury induced by α-GalCer stiff remains to be elucidated. In this study, we employed inescapable electric foot shock as the mode of psychophysical stress and evaluated its effect on α -GalCer-induced hepatitis. Pre-exposure of 12 hours of foot shock stress before α-GalCer administration significantly enhanced α-GalCer-triggered increase in serum alanine aminotransferase levels, followed by increases in both liver caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive hepatocytes, thus indicating that the liver NKT cell-dependent apoptotic response was exacerbated by stress. Foot shock stress also significantly increased both the number of liver NKT cells and Fas expression levels on hepatocytes. Pretreatment with RU-486, a glucocorticoid (GC) receptor antagonist, completely reversed such stress-induced enhancement of the α-GalCer-triggered serum alanine aminotransferase and hepatocyte Fas antigen responses. In contrast, such a reversal effect was not found in the mice pretreated with naloxone, a μ-opioid receptor antagonist, which thus suggests that an elevation of endogenous GCs, but not β-endorpliin, as responsible for such stress-induced aggravation in mouse hepatitis models. In conclusion, foot shock stress-induced elevation of endogenous GCs exacerbates α-GalCer-initiated hepatic apoptosis through the expansion of liver NKT cells and the up-regulation of hepatocyte Fas antigen.

Original languageEnglish
Pages (from-to)1131-1140
Number of pages10
Issue number4
Publication statusPublished - Apr 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology

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