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Sevoflurane-mediated TGF-beta1 signaling in renal proximal tubule cells.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2008 Feb; Vol. 294 (2), pp. F371-8. Date of Electronic Publication: 2007 Dec 05. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Active Transport, Cell Nucleus drug effects
Anesthetics, Inhalation pharmacology
Annexin A5 pharmacology
Antibodies pharmacology
Cell Communication physiology
Cell Line, Transformed
Cell Nucleus metabolism
HSP70 Heat-Shock Proteins metabolism
Humans
Liposomes pharmacology
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3 metabolism
Models, Biological
NF-kappa B metabolism
Phosphatidylserines pharmacology
Phosphorylation drug effects
Proto-Oncogene Proteins c-akt metabolism
Recombinant Proteins pharmacology
Sevoflurane
Signal Transduction drug effects
Smad3 Protein metabolism
Transforming Growth Factor beta1 immunology
Transforming Growth Factor beta1 pharmacology
Tumor Necrosis Factor-alpha pharmacology
Kidney Tubules, Proximal cytology
Methyl Ethers pharmacology
Signal Transduction physiology
Transforming Growth Factor beta1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1931-857X
- Volume :
- 294
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 18057187
- Full Text :
- https://doi.org/10.1152/ajprenal.00277.2007