Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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Effects of the Protein Kinase A Inhibitor KT5720 on Glucagon-Mediated Decrease in Expression of Antioxidant Enzymes

Protein kinase A 억제제인 KT5720이 글루카곤 매개성 항산화 효소의 발현감소에 미치는 영향

  • Oh Soo-Jin (College of Pharmacy, Chungnam National University) ;
  • Jo Jae-Hoon (College of Pharmacy, Chungnam National University) ;
  • Park Chang-Sik (Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kim Sang-Kyum (College of Pharmacy, Chungnam National University) ;
  • Kim Bong-Hee (College of Pharmacy, Chungnam National University)
  • Published : 2006.09.01
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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 $\mu$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 $\mu$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 $\mu$M H89 and attenuated by 0.1 $\mu$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.

Keywords

References

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