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Translocation of protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide synthase activation

Publication ,  Journal Article
Wang, L; Wu, B; Sun, Y; Xu, T; Zhang, X; Zhou, M; Jiang, W
Published in: British Journal of Anaesthesia
January 1, 2010

Background. Previous studies have indicated that protein kinase C (PKC) may enhance endothelial nitric oxide synthase (eNOS) activation, although the detailed mechanism(s) remains unclear. In this study, we investigated the roles of PKC isoforms in regulating propofol-induced eNOS activation in human umbilical vein endothelial cells (HUVECs).Methods. We applied western blot (WB) analysis to investigate the effects of propofol on Ser1177 phosphorylation-dependent eNOS activation in HUVECs. Nitrite (NO 2-) accumulation was measured using the Griess assay. The phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway was examined by WB assay. Propofol-induced translocation of individual PKC isoforms in subcellular fractions in HUVECs was analysed using WB assay.Results. In HUVECs, protocol treatment (1-100 μM) for 10 min induced a concentration-dependent increase in phosphorylation of eNOS at Ser1177. The NO production was also increased accordingly. PKC inhibitors, bisindolylmaleimide I (0.1-1 μM), and staurosporine (20 and 100 nM), effectively blocked propofol-induced eNOS activation and NO production. Further analyses in fractionated endothelial lysate showed that short-term propofol treatment (50 μM) led to translocation of PKC-α, PKC-δ, PKC-ζ, PKC-η, and PKC-ε from cytosolic to membrane fractions, which could also be inhibited by both PKC inhibitors. These data revealed that the differential redistribution of these isozymes is ndispensable for propofol-induced eNOS activation. In addition, Akt was not phosphorylated in response to propofol at Ser473 or Thr 308.Conclusions. Propofol induces the Ser1177 phosphorylation-dependent eNOS activation through the drug-stimulated translocation of PKC isoforms to distinct intracellular sites in HUVECs, which is independent of PI3K/Akt-independent pathway. © The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.

Duke Scholars

Published In

British Journal of Anaesthesia

DOI

EISSN

1471-6771

ISSN

0007-0912

Publication Date

January 1, 2010

Volume

104

Issue

5

Start / End Page

606 / 612

Related Subject Headings

  • Anesthesiology
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

Citation

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Wang, L., Wu, B., Sun, Y., Xu, T., Zhang, X., Zhou, M., & Jiang, W. (2010). Translocation of protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide synthase activation. British Journal of Anaesthesia, 104(5), 606–612. https://doi.org/10.1093/bja/aeq064
Wang, L., B. Wu, Y. Sun, T. Xu, X. Zhang, M. Zhou, and W. Jiang. “Translocation of protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide synthase activation.” British Journal of Anaesthesia 104, no. 5 (January 1, 2010): 606–12. https://doi.org/10.1093/bja/aeq064.
Wang L, Wu B, Sun Y, Xu T, Zhang X, Zhou M, et al. Translocation of protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide synthase activation. British Journal of Anaesthesia. 2010 Jan 1;104(5):606–12.
Wang, L., et al. “Translocation of protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide synthase activation.” British Journal of Anaesthesia, vol. 104, no. 5, Jan. 2010, pp. 606–12. Scopus, doi:10.1093/bja/aeq064.
Wang L, Wu B, Sun Y, Xu T, Zhang X, Zhou M, Jiang W. Translocation of protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide synthase activation. British Journal of Anaesthesia. 2010 Jan 1;104(5):606–612.
Journal cover image

Published In

British Journal of Anaesthesia

DOI

EISSN

1471-6771

ISSN

0007-0912

Publication Date

January 1, 2010

Volume

104

Issue

5

Start / End Page

606 / 612

Related Subject Headings

  • Anesthesiology
  • 3202 Clinical sciences
  • 1103 Clinical Sciences