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Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS.

Publication ,  Journal Article
Li, Z; Carter, JD; Dailey, LA; Huang, Y-CT
Published in: Environ Health Perspect
February 2004

Exposure to excessive vanadium occurs in some occupations and with consumption of some dietary regimens for weight reduction and body building. Because vanadium is vasoactive, individuals exposed to excessive vanadium may develop adverse vascular effects. We have previously shown that vanadyl sulfate causes acute pulmonary vasoconstriction, which could be attributed in part to inhibition of nitric oxide production. In the present study we investigated whether NO inhibition was related to phosphorylation of endothelial nitric oxide synthase (eNOS). VOSO4 produced dose-dependent constriction of pulmonary arteries in isolated perfused lungs and pulmonary arterial rings and a right shift of the acetylcholine-dependent vasorelaxation curve. VOSO4 inhibited constitutive as well as A23187-stimulated NO production. Constitutive NO inhibition was accompanied by increased Thr495 (threonine at codon 495) phosphorylation of eNOS, which would inhibit eNOS activity. Thr495 phosphorylation of eNOS and inhibition of NO were partially reversed by pretreatment with calphostin C, a protein kinase C (PKC) inhibitor. There were no changes in Ser1177 (serine at codon 1177) or tyrosine phosphorylation of eNOS. These results indicate that VOSO4 induced acute pulmonary vasoconstriction that was mediated in part by the inhibition of endothelial NO production via PKC-dependent phosphorylation of Thr495 of eNOS. Exposure to excessive vanadium may contribute to pulmonary vascular diseases.

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Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

February 2004

Volume

112

Issue

2

Start / End Page

201 / 206

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Vanadium Compounds
  • Vanadium
  • Toxicology
  • Threonine
  • Rabbits
  • Phosphorylation
  • Organ Culture Techniques
  • Occupational Exposure
  • Nitric Oxide Synthase
 

Citation

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Li, Z., Carter, J. D., Dailey, L. A., & Huang, Y.-C. (2004). Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS. Environ Health Perspect, 112(2), 201–206. https://doi.org/10.1289/ehp.6477
Li, Zhuowei, Jacqueline D. Carter, Lisa A. Dailey, and Yuh-Chin T. Huang. “Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS.Environ Health Perspect 112, no. 2 (February 2004): 201–6. https://doi.org/10.1289/ehp.6477.
Li Z, Carter JD, Dailey LA, Huang Y-CT. Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS. Environ Health Perspect. 2004 Feb;112(2):201–6.
Li, Zhuowei, et al. “Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS.Environ Health Perspect, vol. 112, no. 2, Feb. 2004, pp. 201–06. Pubmed, doi:10.1289/ehp.6477.
Li Z, Carter JD, Dailey LA, Huang Y-CT. Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS. Environ Health Perspect. 2004 Feb;112(2):201–206.

Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

February 2004

Volume

112

Issue

2

Start / End Page

201 / 206

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Vanadium Compounds
  • Vanadium
  • Toxicology
  • Threonine
  • Rabbits
  • Phosphorylation
  • Organ Culture Techniques
  • Occupational Exposure
  • Nitric Oxide Synthase