Nox4 contributes to the hypoxia-mediated regulation of actin cytoskeleton in cerebrovascular smooth muscle

Maha Coucha, Mohammed Abdelsaid, Weiguo Li, Maribeth H. Johnson, L. Őrfi, Azza B. El-Remessy, Susan C. Fagan, Adviye Ergul

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6 Citations (Scopus)

Abstract

Ischemia/reperfusion and the resulting oxidative/nitrative stress impair cerebral myogenic tone via actin depolymerization. While it is known that NADPH oxidase (Nox) family is a major source of vascular oxidative stress; the extent and mechanisms by which Nox activation contributes to actin depolymerization, and equally important, the relative role of Nox isoforms in this response is not clear. Aim: To determine the role of Nox4 in hypoxia-mediated actin depolymerization and myogenic-tone impairment in cerebral vascular smooth muscle. Main methods: Control and Nox4 deficient (siRNA knock-down) human brain vascular smooth muscle cells (HBVSMC) were exposed to 30-min hypoxia/45-min reoxygenation. Nox2, Nox4, inducible and neuronal nitric oxide synthase (iNOS and nNOS) and nitrotyrosine levels as well as F:G actin were determined. Myogenic-tone was measured using pressurized arteriography in middle cerebral artery isolated from rats subjected to sham, 30-min ischemia/45-min reperfusion or ex-vivo oxygen glucose deprivation in the presence and absence of Nox inhibitors. Results: Nox4 and iNOS expression were significantly upregulated following hypoxia or ischemia/reperfusion. Hypoxia augmented nitrotyrosine levels while reducing F actin. These effects were nullified by inhibiting nitration with epicatechin or pharmacological or molecular inhibition of Nox4. Ischemia/reperfusion impaired myogenic-tone, which was restored by the selective inhibition of Nox4. Conclusion: Nox4 activation in VSMCs contributes to actin depolymerization after hypoxia, which could be the underlying mechanism for myogenic-tone impairment following ischemia/reperfusion.

Original languageEnglish
Pages (from-to)46-54
Number of pages9
JournalLife Sciences
Volume163
DOIs
Publication statusPublished - Oct 15 2016

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Keywords

  • Actin polymerization
  • Hypoxia
  • Ischemia/reperfusion
  • Myogenic tone
  • NADPH oxidase
  • Nox4
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Coucha, M., Abdelsaid, M., Li, W., Johnson, M. H., Őrfi, L., El-Remessy, A. B., Fagan, S. C., & Ergul, A. (2016). Nox4 contributes to the hypoxia-mediated regulation of actin cytoskeleton in cerebrovascular smooth muscle. Life Sciences, 163, 46-54. https://doi.org/10.1016/j.lfs.2016.08.018