system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Anesthetics, Inhalation, Antibodies, Cell Line, Cell Membrane, Humans, Hydrogen Peroxide, Kidney Tubules, Proximal, Necrosis, Phosphatidylserines, Transcription, Genetic, Transforming Growth Factor beta.
user
Does tGF-beta1 release by volatile anesthetics mediate protection against renal proximal tubule cell necrosis? Context: 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-beta1 (TGF-beta1), a cytokine with antinecrotic properties. 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-beta1 into the cell culture media. Exogenous TGF-beta1 induced protection and neutralizing TGF-beta1 antibody prevented the cytoprotection by volatile anesthetics against hydrogen peroxide-induced HK-2 cell necrosis.
assistant
Volatile anesthetics induce a cytoprotective signaling cascade in proximal tubule cells via membrane externalization of PS initiating TGF-beta1-mediated cytoprotection. Final Decision: yes