Water-deprivation-induced expression of neuronal nitric oxide synthase in the hypothalamic paraventricular nucleus of rat

2008 ◽  
Vol 86 (6) ◽  
pp. 1371-1379 ◽  
Author(s):  
Vitaly Ryu ◽  
Jong-Ho Lee ◽  
Ji Won Um ◽  
Sang Bae Yoo ◽  
Jisun Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Paraventricular Nucleus ◽  
Water Deprivation ◽  
Neuronal Nitric Oxide Synthase ◽  
Hypothalamic Paraventricular Nucleus ◽  
Induced Expression ◽  
Oxide Synthase

Refeeding-induced expression of neuronal nitric oxide synthase in the rat paraventricular nucleus

2005 ◽  
Vol 1048 (1-2) ◽  
pp. 185-192 ◽  
Author(s):  
Jeong Won Jahng ◽  
Joo Young Lee ◽  
Sang Bae Yoo ◽  
Yun Mi Kim ◽  
Vitaly Ryu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Paraventricular Nucleus ◽  
Neuronal Nitric Oxide Synthase ◽  
Induced Expression ◽  
Oxide Synthase

scholarly journals Anteroventral third ventricle (AV3V) lesion affects hypothalamic neuronal nitric oxide synthase (nNOS) expression following water deprivation

2011 ◽  
Vol 86 (3-4) ◽  
pp. 239-245 ◽  
Author(s):  
Fábio Alves Aguila ◽  
Gabriela Ravanelli Oliveira-Pelegrin ◽  
Song Tieng Yao ◽  
David Murphy ◽  
Maria José Alves Rocha
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Water Deprivation ◽  
Third Ventricle ◽  
Neuronal Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Nnos Expression

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.

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