Inhibition of Superoxide Generation from Neuronal Nitric Oxide Synthase by Heat Shock Protein 90:  Implications in NOS Regulation†

Biochemistry ◽  
2002 ◽  
Vol 41 (34) ◽  
pp. 10616-10622 ◽  
Author(s):  
Yao Song ◽  
A. J. Cardounel ◽  
Jay L. Zweier ◽  
Yong Xia
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Nitric Oxide Synthase ◽  
Heat Shock Protein ◽  
Neuronal Nitric Oxide Synthase ◽  
Heat Shock Protein 90 ◽  
Superoxide Generation ◽  
Oxide Synthase

scholarly journals Heat Shock Protein 90 Mediates the Balance of Nitric Oxide and Superoxide Anion from Endothelial Nitric-oxide Synthase

2001 ◽  
Vol 276 (21) ◽  
pp. 17621-17624 ◽  
Author(s):  
Kirkwood A. Pritchard ◽  
Allan W. Ackerman ◽  
Eric R. Gross ◽  
David W. Stepp ◽  
Yang Shi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Nitric Oxide Synthase ◽  
Heat Shock Protein ◽  
Endothelial Nitric Oxide Synthase ◽  
Superoxide Anion ◽  
Heat Shock Protein 90 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Heat shock protein 90 modulates endothelial nitric oxide synthase activity and vascular reactivity in the newborn piglet pulmonary circulation

2007 ◽  
Vol 292 (6) ◽  
pp. L1515-L1525 ◽  
Author(s):  
Judy L. Aschner ◽  
Susan L. Foster ◽  
Mark Kaplowitz ◽  
Yongmei Zhang ◽  
Heng Zeng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Nitric Oxide Synthase ◽  
Heat Shock Protein ◽  
Pulmonary Circulation ◽  
Endothelial Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Heat Shock Protein 90 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Heat shock protein 90 (Hsp90) binding to endothelial nitric oxide synthase (eNOS) is an important step in eNOS activation. The conformational state of bound Hsp90 determines whether eNOS produces nitric oxide (NO) or superoxide (O2•−). We determined the effects of the Hsp90 antagonists geldanamycin (GA) and radicicol (RA) on basal and ACh-stimulated changes in vessel diameter, cGMP production, and Hsp90:eNOS coimmunoprecipitation in piglet resistance level pulmonary arteries (PRA). In perfused piglet lungs, we evaluated the effects of GA and RA on ACh-stimulated changes in pulmonary arterial pressure (Ppa) and perfusate accumulation of stable NO metabolites (NOx−). The effects of GA and RA on ACh-stimulated O2•− generation was investigated in cultured pulmonary microvascular endothelial cells (PMVEC) by dihydroethidine (DHE) oxidation and confocal microscopy. Hsp90 inhibition with GA or RA reduced ACh-mediated dilation, abolished the ACh-stimulated increase in cGMP, and reduced eNOS:Hsp90 coprecipitation. GA and RA also inhibited the ACh-mediated changes in Ppa and NOx− accumulation rates in perfused lungs. ACh increased the rate of DHE oxidation in PMVEC pretreated with GA and RA but not in untreated cells. The cell-permeable superoxide dismutase mimetic M40401 reversed GA-mediated inhibition of ACh-induced dilation in PRA. We conclude that Hsp90 is a modulator of eNOS activity and vascular reactivity in the newborn piglet pulmonary circulation. Uncoupling of eNOS with GA or RA inhibits ACh-mediated dilation by a mechanism that involves O2•− generation.

Sign in / Sign up

Export Citation Format

Share Document