Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several volatile anesthetics, including sevoflurane, protect against renal ischemia-reperfusion injury in vivo by reducing necrosis and inflammation. Furthermore, in cultured renal tubule cells, sevoflurane directly induced the phosphorylation of the cytoprotective kinases (ERK and Akt), upregulated 70-kDa heat shock protein (HSP70), and attenuated nuclear translocation of the proinflammatory transcription factor NF-kappaB. It has been shown that sevoflurane increases the release of transforming growth factor-beta1 (TGF-beta1) in human proximal tubule (HK-2) cells via externalization of plasma membrane phosphatidylserine (PS), and this increase in TGF-beta1 protected HK-2 cells against hydrogen peroxide-mediated necrosis. In this study, we aimed to determine whether the sevoflurane-mediated phosphorylation of ERK and Akt, induction of HSP70, and reduction in NF-kappaB activation are due to TGF-beta1 receptor-mediated signaling after PS externalization in HK-2 cells. Exogenous TGF-beta1 and a liposome mixture containing PS mimicked sevoflurane-mediated ERK and Akt phosphorylation and HSP70 induction in HK-2 cells. Sevoflurane and TGF-beta1 caused the nuclear translocation of the SMAD3 transcription factor in HK-2 cells. Furthermore, a neutralizing TGF-beta1 antibody or exogenous annexin V to bind PS prevented sevoflurane-induced ERK and Akt phosphorylation and HSP70 induction in HK-2 cells. Finally, a TGF-beta1 antibody and annexin V attenuated the reduction in nuclear translocation of NF-kappaB by sevoflurane. Therefore, we demonstrate in this study that sevoflurane-mediated cytoprotective and anti-inflammatory effects in HK-2 cells are at least partially due to the externalization of PS and activation of TGF-beta1 signaling pathways.
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PMID:Sevoflurane-mediated TGF-beta1 signaling in renal proximal tubule cells. 1805 87

We previously demonstrated that several clinically utilized volatile anesthetics including sevoflurane protected against renal ischemia-reperfusion (IR) injury by reducing necrosis and inflammation in vivo. We also demonstrated that volatile anesthetics produced direct anti-necrotic and anti-inflammatory effects in cultured renal tubules via mechanisms involving the externalization of phosphatidylserine and subsequent release of transforming growth factor (TGF)-beta1. In this study, we tested the hypothesis that volatile anesthetic-mediated renal protection requires TGF-beta1 and SMAD3 signaling in vivo. We subjected TGF-beta1+/+, TGF-beta1+/-, SMAD3+/+, or SMAD3-/- mice to renal IR under anesthesia with pentobarbital sodium or with sevoflurane. Although TGF-beta1+/+ and SMAD3+/+ mice were significantly protected against renal IR injury under sevoflurane anesthesia with reduced necrosis and inflammation, TGF-beta1+/- mice and SMAD3-/- mice were not protected against renal IR with sevoflurane. Furthermore, a neutralizing TGF-beta1 antibody blocked renal protection with sevoflurane in TGF-beta1+/+ mice. Sevoflurane caused nuclear translocation of SMAD3 and reduced the TNF-alpha-induced nuclear translocation of NF-kappaB in primary cultures of proximal tubules from TGF-beta1+/+ but not in TGF-beta1+/- mice. Finally, sevoflurane protected against necrosis induced with hydrogen peroxide in primary cultures of proximal tubules from TGF-beta1+/+ mice or SMAD3+/+ mice but not in proximal tubules from TGF-beta1+/- or SMAD3-/- mice. Therefore, we demonstrate in this study that sevoflurane-mediated renal protection in vivo requires the TGF-beta1-->SMAD3 signaling pathway.
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PMID:Sevoflurane protects against renal ischemia and reperfusion injury in mice via the transforming growth factor-beta1 pathway. 1843 84