Osmotic stress induces loss of glutathione and increases the sensitivity to oxidative stress in H9c2 cardiac myocytes.
It has been observed that H9c2 cardiac cells cultured in physiologic solutions exhibit delayed cell death after repeated medium replacements, of which the cause was the relatively mild osmotic challenges during the renewal of the culture medium. Interestingly, the cell damage was associated with altered intracellular GSH homeostasis. Therefore, this study attempted to elucidate the effects of osmotic stress on GSH metabolism. In cells subjected to osmotic stress by lowering the NaCl concentration of the medium, the cell swelling was rapidly counterbalanced, but the intracellular GSH content was significantly lower in 3 h. Meanwhile, the ratio of GSH-to-GSSG was not affected. As expected, osmotic stress also increased the sensitivity to H(2)O(2), which was attributable to the decrease of GSH content. The decrease of GSH content was similarly evident when the synthetic pathways of GSH were blocked by BSO or acivicin. It was concluded that osmotic stress induced the decrease of intracellular GSH content by increased consumption and this loss of GSH rendered the cells susceptible to a subsequent oxidative stress.
Lee
Jun Whee
JW
Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
Ko
Young Eun
YE
Lee
In Hye
IH
Lee
Hye Kyung
HK
Kim
Hae Won
HW
Kim
Young-hoon
YH
D000818:Animals; D002460:Cell Line; D005978:Glutathione / Q000172:deficiency* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats
D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione