Background/Aims: We have previously demonstrated that clinically utilized volatile anesthetics protect against renal ischemia reperfusion injury in rats in vivo and reduce necrosis in vitro via activation of ERK and Akt and by upregulating HSP70. In this study, we further deciphered the upstream cellular signaling mechanism(s) of volatile anesthetic-mediated antinecrotic effects in vitro. We hypothesized that volatile anesthetics perturb the structure of the plasma membrane lipid bilayer, causing externalization of phosphatidylserine (PS) to the outer surface on renal tubule cells leading to the increased generation of transforming growth factor-β1 (TGF-β1), a cytokine with antinecrotic properties. Methods and Results: In human proximal tubule (HK-2) cell culture, 16-hour exposure to volatile anesthetics (isoflurane, halothane, sevoflurane) caused membrane externalization of PS detected by positive annexin-V staining and increased the release of TGF-β1 into the cell culture media. Exogenous TGF-β1 induced protection and neutralizing TGF-β1 antibody prevented the cytoprotection by volatile anesthetics against hydrogen peroxide-induced HK-2 cell necrosis. Conclusions: Volatile anesthetics induce a cytoprotective signaling cascade in proximal tubule cells via membrane externalization of PS initiating TGF-β1-mediated cytoprotection.

Keywords:
Acute renal failure, Isoflurane, Halothane, Desflurane, Sevoflurane, Lactate dehydrogenase, Phosphatidylserine
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© 2007 S. Karger AG, Basel
2007
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