scholarly journals Regulatory Role of Glu546 in Flavin Mononucleotide — Heme Electron Transfer in Human Inducible Nitric Oxide Synthase

2013 ◽  
Vol 52 (9) ◽  
pp. 4795-4801 ◽  
Author(s):  
Wenbing Li ◽  
Li Chen ◽  
Changyuan Lu ◽  
Bradley O. Elmore ◽  
Andrei V. Astashkin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Transfer ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Regulatory Role ◽  
Flavin Mononucleotide ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

N-Glycosylation at Asn695 might suppress inducible nitric oxide synthase activity by disturbing electron transfer

2020 ◽  
Vol 52 (12) ◽  
pp. 1360-1372
Author(s):  
Jianghong Yan ◽  
Fei-Fei Shang ◽  
An He ◽  
Shupeng Hu ◽  
Suxin Luo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Transfer ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Conformational Changes ◽  
Binding Domain ◽  
Flavin Mononucleotide ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Abstract Inducible nitric oxide synthase (iNOS) plays critical roles in the inflammatory response and host defense. Previous research on iNOS regulation mainly focused on its gene expression level, and much less is known about the regulation of iNOS function by N-glycosylation. In this study, we report for the first time that iNOS is N-glycosylated in vitro and in vivo. Mass spectrometry studies identified Asn695 as an N-glycosylation site of murine iNOS. Mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity. The essence of nitric oxide synthase catalytic reaction is electron transfer process, which involves a series of conformational changes, and the linker between the flavin mononucleotide-binding domain and the flavin adenine dinucleotide-binding domain plays vital roles in the conformational changes. Asn695 is part of the linker, so we speculated that attachment of N-glycan to the Asn695 residue might inhibit activity by disturbing electron transfer. Indeed, our NADPH consumption results demonstrated that N-glycosylated iNOS consumes NADPH more slowly. Taken together, our results indicate that iNOS is N-glycosylated at its Asn695 residue and N-glycosylation of Asn695 might suppress iNOS activity by disturbing electron transfer.

Monocyte Inducible Nitric Oxide Synthase in Multiple Sclerosis: Regulatory Role of Nitric Oxide

Nitric Oxide ◽  
1997 ◽  
Vol 1 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Natalia López-Moratalla ◽  
Álvaro González ◽  
M.Soledad Aymerich ◽  
Marı́a J. López-Zabalza ◽  
Rubén Pı́o ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Regulatory Role ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Geldanamycin inhibits hemorrhage-induced increases in caspase-3 activity: role of inducible nitric oxide synthase

2007 ◽  
Vol 103 (3) ◽  
pp. 1045-1055 ◽  
Author(s):  
Juliann G. Kiang ◽  
Phillip D. Bowman ◽  
Xinyue Lu ◽  
Yansong Li ◽  
Brian W. Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Caspase 3 ◽  
Gene Transfection ◽  
Organ Injury ◽  
Molecular Events ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Hemorrhage has been shown to increase inducible nitric oxide synthase (iNOS) and deplete ATP levels in tissues and geldanamycin limits both processes. Moreover, it is evident that inhibition of iNOS reduces caspase-3 and increases survival. Thus we sought to identify the molecular events responsible for the beneficial effect of geldanamycin. Hemorrhage in mice significantly increased caspase-3 activity and protein while treatment with geldanamycin significantly limited these increases. Similarly, geldanamycin inhibited increases in proteins forming the apoptosome (a complex of caspase-9, cytochrome c, and Apaf-1). Modulation of the expression of iNOS by iNOS gene transfection or siRNA treatment demonstrated that the level of iNOS correlates with caspase-3 activity. Our data indicate that geldanamycin limits caspase-3 expression and protects from organ injury by suppressing iNOS expression and apoptosome formation. Geldanamycin, therefore, may prove useful as an adjuvant in fluids used to treat patients suffering blood loss.

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