Plasma membrane-associated endothelial nitric oxide synthase and activity in aging rat aortic vascular endothelia markedly decline with age.

Abstract:

:The mechanisms leading to the age-related loss of endothelial nitric oxide (NO) and NO-dependent vasodilation remain largely unknown. Freshly isolated endothelium from young (6 months) and old (36 months) F344xBrN rats were analyzed for endothelial nitric oxide synthase (eNOS) protein, its subcellular distribution, and association with regulatory proteins. Results show that both vessel ring vasoreactivity and A23187-induced eNOS activity in isolated endothelial cells significantly (p < or = 0.05) declined with age. Levels of cGMP, a reliable marker for NO bioactivity also declined significantly (p < or = 0.01). However, no change in overall eNOS protein was evident. Subcellular fractionation studies revealed an age-related loss in active, plasma membrane-bound eNOS relative to eNOS in the Golgi/cytosol of the endothelium. Plasma membrane-associated eNOS in aged endothelium was also less complexed with the activating proteins Hsp90 and Akt and more associated with to caveolin-1, which inhibits eNOS activity. These results suggest that age-dependent loss of NO may be partly caused by differences in eNOS subcellular distribution and its association with inhibitory proteins.

journal_name

Arch Biochem Biophys

authors

Smith AR,Visioli F,Hagen TM

doi

10.1016/j.abb.2006.02.017

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

100-5

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(06)00070-1

journal_volume

454

pub_type

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