Inhibition of nitric oxide synthase prevents magnesium-free-induced epileptiform activity in guinea-pig piriform cortex neurones in vitro

1997 ◽  
Vol 355 (4) ◽  
pp. 452-456 ◽  
Author(s):  
V. Libri ◽  
Rosamaria Santarelli ◽  
Steven Nisticò ◽  
Gian Battista Azzena
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Guinea Pig ◽  
Epileptiform Activity ◽  
Piriform Cortex ◽  
Oxide Synthase

Nitric oxide synthase activity in the hippocampus, frontal cerebral cortex, and cerebellum of the guinea pig: Ontogeny and in vitro ethanol exposure

Alcohol ◽  
1995 ◽  
Vol 12 (4) ◽  
pp. 329-333 ◽  
Author(s):  
James F. Brien ◽  
James D. Reynolds ◽  
Michael A. Cunningham ◽  
Ann M. Parr ◽  
Sarah Waddock ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Cortex ◽  
Nitric Oxide Synthase ◽  
Guinea Pig ◽  
Ethanol Exposure ◽  
Frontal Cerebral Cortex ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

Nitric oxide synthase inhibitors 7- and 6-nitroindazole relax smooth muscle in vitro

1994 ◽  
Vol 256 (1) ◽  
pp. R5-R6 ◽  
Author(s):  
Andrew D. Medhurst ◽  
Carol Greenlees ◽  
Andrew A. Parsons ◽  
Susan J. Smith
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitors ◽  
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.

scholarly journals Modulation of guinea-pig cardiac L-type calcium current by nitric oxide synthase inhibitors

1998 ◽  
Vol 506 (3) ◽  
pp. 639-651 ◽  
Author(s):  
Maria Pia Gallo ◽  
Dario Ghigo ◽  
Amalia Bosia ◽  
Giuseppe Alloatti ◽  
Costanzo Costamagna ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Guinea Pig ◽  
Calcium Current ◽  
Nitric Oxide Synthase Inhibitors ◽  
Oxide Synthase
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