Altered endothelial nitric oxide synthase targeting and conformation and caveolin-1 expression in the diabetic kidney

Radko Komers, William E. Schutzer, John F. Reed, Jessie N. Lindsley, Terry T. Oyama, David C. Buck, Scott L. Mader, Sharon Anderson

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Experimental diabetes is associated with complex changes in renal nitric oxide (NO) bioavailability. We explored the effect of diabetes on renal cortical protein expression of endothelial NO synthase (eNOS) with respect to several determinants of its enzymatic function, such as eNOS expression, membrane localization, phosphorylation, and dimerization, in moderately hyperglycemic streptozotocin-induced diabetic rats compared with nondiabetic control rats and diabetic rats with intensive insulin treatment to achieve near-normal metabolic control. We studied renal cortical expression and localization of caveolin-1 (CAV-1), an endogenous modulator of eNOS function. Despite similar whole-cell eNOS expression in all groups, eNOS monomer and dimer in membrane fractions were reduced in moderately hyperglycemic diabetic rats compared with control rats; the opposite trend was apparent in the cytosol. Stimulatory phosphorylation of eNOS (Ser1177) was also reduced in moderately hyperglycemic diabetic rats. eNOS colocalized and interacted with CAV-1 in endothelial cells throughout the renal vascular tree both in control and moderately hyperglycemic diabetic rats. However, the abundance of membrane-localized CAV-1 was decreased in diabetic kidneys. Intensive insulin treatment reversed the effects of diabetes on each of these parameters. In summary, we observed diabetes-mediated alterations in eNOS and CAV-1 expression that are consistent with the view of decreased bioavailability of renal eNOS-derived NO.

Original languageEnglish (US)
Pages (from-to)1651-1659
Number of pages9
JournalDiabetes
Volume55
Issue number6
DOIs
StatePublished - 2006

Fingerprint

Caveolin 1
Nitric Oxide Synthase Type III
Nitric Oxide Synthase
Kidney
Biological Availability
Membranes
Nitric Oxide
Endothelial Cells
Phosphorylation
Insulin
Dimerization
Streptozocin
Cytosol
Blood Vessels

Keywords

  • CAV-1, caveolin-1
  • eNOS, endothelial nitric oxide synthase
  • NOS, nitric oxide synthase

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Altered endothelial nitric oxide synthase targeting and conformation and caveolin-1 expression in the diabetic kidney. / Komers, Radko; Schutzer, William E.; Reed, John F.; Lindsley, Jessie N.; Oyama, Terry T.; Buck, David C.; Mader, Scott L.; Anderson, Sharon.

In: Diabetes, Vol. 55, No. 6, 2006, p. 1651-1659.

Research output: Contribution to journalArticle

Komers, R, Schutzer, WE, Reed, JF, Lindsley, JN, Oyama, TT, Buck, DC, Mader, SL & Anderson, S 2006, 'Altered endothelial nitric oxide synthase targeting and conformation and caveolin-1 expression in the diabetic kidney', Diabetes, vol. 55, no. 6, pp. 1651-1659. https://doi.org/10.2337/db05-1595
Komers, Radko ; Schutzer, William E. ; Reed, John F. ; Lindsley, Jessie N. ; Oyama, Terry T. ; Buck, David C. ; Mader, Scott L. ; Anderson, Sharon. / Altered endothelial nitric oxide synthase targeting and conformation and caveolin-1 expression in the diabetic kidney. In: Diabetes. 2006 ; Vol. 55, No. 6. pp. 1651-1659.
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