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http://dx.doi.org/10.5352/JLS.2013.23.11.1342

Protection of Primary Cultured Mouse Hepatocytes from Chemical Hypoxia-induced Injury by Hydrogen Sulfide  

Lee, Min Young (Department of Molecular Physiology, College of Pharmacy, Kyungpook National University)
Publication Information
Journal of Life Science / v.23, no.11, 2013 , pp. 1342-1350 More about this Journal
Abstract
We examined the effect of hydrogen sulfide ($H_2S$) in chemical hypoxia-induced injury in mouse hepatocytes. Cell viability was significantly decreased by cobalt chloride ($CoCl_2$), a well-known hypoxia mimetic agent in a time- and dose- dependent manner. Sodium hydrosulfide (NaHS, a donor of $H_2S$) pretreatment before exposure to $CoCl_2$ significantly attenuated the $CoCl_2$-induced decrease of cell viability. $CoCl_2$ treatment resulted in an increase of intracellular ROS generation, which is inhibited by NaHS or N-acetyl-cysteine (NAC, a ROS scavenger), and p38 MAPK phosphorylation, which is also blocked by NaHS or NAC. The $CoCl_2$-induced increase of the Bax/Bcl-2 ratio was attenuated by NaHS, NAC, and SB 203580 (p38 MAPK inhibitor). The $CoCl_2$-induced decrease of cell viability was also attenuated by NaHS, NAC, and SB 203580 pretreatment. Additionally, NaHS inhibited the $CoCl_2$-induced COX-2. Similar to the effect of NaHS, NAC blocked $CoCl_2$-induced COX-2 expression. Furthermore, NS-398 (a selective COX-2 inhibitor) attenuated not only the $CoCl_2$-induced increase of the Bax/Bcl-2 ratio, it also decreased cell viability. Taken together, $H_2S$ protects primary cultured mouse hepatocytes against $CoCl_2$-induced cell injury through inhibition of the ROS-activated p38 MAPK cascade and the COX-2 pathway.
Keywords
Hydrogen sulfide; cobalt chloride; chemical hypoxia; mouse hepatocytes;
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