Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-alpha-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression.
Liver injury accompanied by apoptosis of hepatocytes was provoked in mice by an intravenous injection of recombinant tumor necrosis factor-alpha (rTNF-alpha) (1.0 microg/kg) together with an intraperitoneal injection of D-galactosamine (D-gal) (500 mg/kg). Injection of various doses of dibutyryl cAMP (DBcAMP) protected mice from TNF-alpha/D-gal-induced liver injury as assessed by serum alanine aminotransferase (ALT) levels, histological examination and DNA fragmentation. DBcAMP significantly enhanced the Hsp70 expression in the hepatocytes of D-gal/TNF-alpha-injected mice in close correlation with suppression of liver injury. DBcAMP induced Hsp70 expression in the hepatocyte in vitro. These results suggest that increase in Hsp70 expression by DBcAMP is involved in protective mechanisms by DBcAMP against TNF-alpha-induced liver injury in D-gal-sensitized mice.
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
M
M
Takano
T
T
Arai
Y
Y
Mokuno
H
H
Nishimura
Y
Y
Nimura
Y
Y
Yoshikai
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005688:Galactosamine / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007275:Injections, Intravenous; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*
D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003994:Bucladesine; D005688:Galactosamine