Insulin resistance does not diminish eNOS expression, phosphorylation, or binding to HSP-90

David J Fulton, M. Brennan Harris, Bruce E. Kemp, Richard C Venema, Mario B Marrero, David W Stepp

Research output: Contribution to journalArticle

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Abstract

Previously, using an animal model of syndrome X, the obese Zucker rat (OZR), we documented impaired endothelium-dependent vasodilation. The aim of this study was to determine whether reduced expression or altered posttranslational regulation of endothelial nitric oxide synthase (eNOS) underlies the vascular dysfunction in OZR rats. There was no significant difference in the relative abundance of eNOS in hearts, aortas, or skeletal muscle between lean Zucker rats (LZR) and OZR regardless of age. There was no difference in eNOS mRNA levels, as determined by real-time PCR, between LZR and OZR. The inability of insulin resistance to modulate eNOS expression was also documented in two additional in vivo models, the ob/ob mouse and the fructose-fed rat, and in vitro via adenoviral expression of protein tyrosine phosphatase 1B in endothelial cells. We next investigated whether changes in the acute posttranslational regulation of eNOS occurs with insulin resistance. Phosphorylation of eNOS at S632 (human S633) and T494 was not different between LZR and OZR; however, phosphorylation of S1176 was significantly enhanced in OZR. Phosphorylation of S1176 was not different in the ob/ob mouse or in fructose-fed rats. The association of heat shock protein 90 with eNOS, a key regulatory step controlling nitric oxide and aberrant O2- production, was not different between OZR and LZR. Taken together, these results suggest that changes in eNOS expression or posttranslation regulation do not underlie the vascular dysfunction seen with insulin resistance and that other mechanisms, such as altered localization, reduced availability of cofactors, substrates, and the elevated production of O2-, may be responsible.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number6 56-6
DOIs
StatePublished - Dec 1 2004

Fingerprint

Zucker Rats
Nitric Oxide Synthase Type III
Insulin Resistance
Phosphorylation
Fructose
Blood Vessels
Non-Receptor Type 1 Protein Tyrosine Phosphatase
HSP90 Heat-Shock Proteins
Vasodilation
Endothelium
Aorta
Real-Time Polymerase Chain Reaction
Myocardium
Nitric Oxide
Skeletal Muscle
Endothelial Cells
Animal Models

Keywords

  • Obesity
  • Syndrome X
  • Zucker

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Insulin resistance does not diminish eNOS expression, phosphorylation, or binding to HSP-90. / Fulton, David J; Harris, M. Brennan; Kemp, Bruce E.; Venema, Richard C; Marrero, Mario B; Stepp, David W.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 287, No. 6 56-6, 01.12.2004.

Research output: Contribution to journalArticle

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