|
KMID : 0893320060210030245
|
|
Journal of Environmental Toxicology
2006 Volume.21 No. 3 p.245 ~ p.253
|
|
|
Effects of the Protein Kinase A Inhibitor KT5720 on Glucagon-Mediated Decrease in Expression of Antioxidant Enzymes
|
|
Oh Soo-Jin
Park Chang-Sik
Kim Sang-Kyum
Kim Bong-Hee
Jo Jae-Hoon
|
|
|
Abstract
|
|
|
|
We reported previously that glucagon decreased alpha- and pi-class glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEN) protein levels in primary cultured rat hepatocytes. The present study examines the effects of Protein kinase A (PKA) inhibitor, KT5720, on the glucagon-mediated decrease in expression of GSTs and mEN. To assess cell viability. lactate dehydrogenase release and MTT activity were examined in hepatocytes treated KT5720. Cell viability was significantly decreased in a concentration dependent manner after incubation with KT5720 at the concentrations of 1 M or above for 24 h, which was inhibited by the cytochrome P450 inhibitor SKF-525A. In contrast, another PKA inhibitor H89 (up to 25 M) was not toxic to hepatocytes. The glucagon-mediated decrease in expression of alpha- and pi-class GSTs and mEH was completely inhibited by 25 M H89 and attenuated by 0.1 M KT5720. This study demonstrates that KT5720 may cause cytotoxicity in rat hepatocytes through cytochrome P450-dependent bioactivation. The present study implicates PKA in mediating the inhibitory effect of glucagon on expression of alpha- and pi- class GSTs and mEH.
|
|
|
KEYWORD
|
|
|
KT5720, glucagon, protein kinase A, glutathione S-transferase, microsomal epoxide hydrolase
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|