scholarly journals Neuronal nitric oxide synthase regulation of skeletal muscle functional hyperemia: exercise training and moderate compensated heart failure

Nitric Oxide ◽  
2018 ◽  
Vol 74 ◽  
pp. 1-9 ◽  
Author(s):  
Daniel M. Hirai ◽  
Steven W. Copp ◽  
Scott K. Ferguson ◽  
Clark T. Holdsworth ◽  
K. Sue Hageman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Exercise Training ◽  
Neuronal Nitric Oxide Synthase ◽  
Functional Hyperemia ◽  
Synthase Regulation ◽  
Oxide Synthase

scholarly journals Effects of chronic heart failure on neuronal nitric oxide synthase-mediated control of microvascular O2pressure in contracting rat skeletal muscle

2012 ◽  
Vol 590 (15) ◽  
pp. 3585-3596 ◽  
Author(s):  
Steven W. Copp ◽  
Daniel M. Hirai ◽  
Scott K. Ferguson ◽  
Clark T. Holdsworth ◽  
Timothy I. Musch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Rat Skeletal Muscle ◽  
Oxide Synthase

Abstract 085: CHIP: E3 Ubiquitin Ligase Mediates Proteasomal Degradation of Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus of Rats with Heart Failure

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Neeru M Sharma ◽  
Kenichi Katsurada ◽  
Xuefei Liu ◽  
Kaushik P Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Nitric Oxide Synthase ◽  
Paraventricular Nucleus ◽  
Ubiquitin Ligase ◽  
Protein A ◽  
Neuronal Nitric Oxide Synthase ◽  
Proteasomal Degradation ◽  
Oxide Synthase

The exaggerated sympathetic drive is a characteristic of heart failure (HF) due to reduced neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN). Previously we have shown that there were increased accumulation of nNOS-ubiquitin (nNOS-Ub) conjugates in the PVN of rats with HF (1.0±0.05 Sham vs. 1.29±0.06 HF) due to the increased levels of PIN (a protein inhibitor of nNOS, known to dissociate nNOS dimers into monomers) (0.76±0.10 Sham vs. 1.12±0.09 HF) and decreased levels of tetrahydrobiopterin (BH4): a cofactor required for stabilization of nNOS dimers (0.62±0.02 Sham vs. 0.44±0.03 HF). We also showed that there is blunted nitric oxide-mediated inhibition of sympathetic tone via the PVN in HF. Here we examined whether CHIP(C-terminus of Hsp70 -interacting protein), a chaperone-dependent E3 ubiquitin-protein isopeptide ligase known to ubiquitylate Hsp90-chaperoned proteins could act as an ubiquitin ligase for nNOS in the PVN. Immunofluorescence studies revealed colocalization of nNOS and CHIP in the PVN indicating their possible interaction. CHIP expression was increased by 50% in the PVN of rats with HF(0.96±0.08 Sham vs.1.44±0.10* HF). It is shown that Hsp90 protects nNOS from ubiquitination while Hsp70 promotes the ubiquitination and degradation. We observed significant upregulation of Hsp70 (0.49±0.03 Sham vs. 0.65±0.02* HF) with a trend toward the decrease in Hsp90 expression (0.90±0.07 Sham vs. 0.71±0.06 HF). The opposing effects of the two chaperones could account for the increased CHIP-mediated ubiquitination and degradation of dysfunctional nNOS monomers in the PVN of rats with HF. Furthermore, neuronal NG108-15 cell line transfected with the pCMV3-CHIP-GFP spark (CHIP overexpression plasmid) showed approximately 74% increase in CHIP with concomitant 49% decrease in nNOS expression. In vitro ubiquitination assay in NG108 cells transfected with pCMV-(HA-Ub) 8 and pCMV3-CHIP-GFP spark plasmid reveal increased HA-Ub-nNOS conjugates (1.13 ± 0.09 Scramble vs. 1.65 ± 0.12* CHIP plasmid). Taken together, our results identify CHIP as an E3 ligase for ubiquitination of dysfunctional nNOS and CHIP expression is augmented during HF leading to increased proteasomal degradation of nNOS in the PVN.

Decreased gene expression of neuronal nitric oxide synthase in hypothalamus and brainstem of rats in heart failure

1996 ◽  
Vol 734 (1-2) ◽  
pp. 109-115 ◽  
Author(s):  
Kaushik. P. Pate ◽  
Kun Zhang ◽  
Irving H. Zucker ◽  
Teresa L. Krukoff
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Oxide Synthase

scholarly journals Skeletal muscle glucose uptake during treadmill exercise in neuronal nitric oxide synthase-μ knockout mice

2016 ◽  
Vol 310 (10) ◽  
pp. E838-E845 ◽  
Author(s):  
Yet Hoi Hong ◽  
Christine Yang ◽  
Andrew C. Betik ◽  
Robert S. Lee-Young ◽  
Glenn K. McConell
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Glucose Uptake ◽  
Neuronal Nitric Oxide Synthase ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Skeletal Muscle Contraction ◽  
Skeletal Muscle Glucose Uptake ◽  
Oxide Synthase

Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ+/+ and nNOSμ−/− mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 ± 0.6 vs. 15.9 ± 0.9 min for nNOSμ+/+ and nNOSμ−/−, respectively, P > 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSμ−/− mice, and exercise increased NOS activity only in nNOSμ+/+ mice (4.4 ± 0.3 to 5.2 ± 0.4 pmol·mg−1·min−1, P < 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSμ−/− than in nNOSμ+/+ mice ( P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSμ−/− mice. In conclusion, nNOSμ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSμ−/− mice may be due to compensatory increases in AMPK activation.

Role of Neuronal Nitric Oxide Synthase in Modulating Microvascular and Contractile Function in Rat Skeletal Muscle

2011 ◽  
Vol 18 (6) ◽  
pp. 501-511 ◽  
Author(s):  
STEVEN W. COPP ◽  
DANIEL M. HIRAI ◽  
SCOTT K. FERGUSON ◽  
TIMOTHY I. MUSCH ◽  
DAVID C. POOLE
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Contractile Function ◽  
Neuronal Nitric Oxide Synthase ◽  
Rat Skeletal Muscle ◽  
Oxide Synthase
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