Author | Tulis, David A. | |
Date Accessioned | 2013-04-05T19:29:40Z | |
Date Available | 2013-04-05T19:29:40Z | |
Date of Issue | 2011 | |
Identifier (Citation) | International Journal of Biomedical Research; 2:9 p. 499-507 | en_US |
Identifier (URI) | http://hdl.handle.net/10342/4141 | |
Description | Efficient electron transfer and conversion of L-arginine to L-citrulline and nitric oxide
(NO●) by neuronal nitric oxide synthase (nNOS) requires calmodulin (CaM) binding. The
present study focused on electron transfer ability of resting state CaM-free nNOS in
presence of dinitrobenzene isomers (DNBs). NADPH oxidation (NADPHox) and acetylated cytochrome-c reduction (AcCyt-cred) catalyzed by nNOS and the CaM binding sequencedeficient nNOS reductase construct (nNOS-FP) were estimates of total electron flux and O2● production, respectively. All the DNBs (o-, m-, p-) independently stimulated rates of NADPHox by CaM-free nNOS and by nNOS-FP in isomer- and concentration-dependent manner. Blocking nNOS heme by imidazole or L-arginine did not affect CaM-free nNOS catalyzed NADPHox stimulated by DNBs. This stimulated electron flux by DNBs did not support NO● formation by CaM-free nNOS. The DNBs, like FeCN, extract electrons from both FMN and FAD of the nNOS reductase domain. All three DNBs greatly stimulated nNOS and nNOS-FP catalyzed AcCyt-cred that was significantly inhibited by SOD demonstrating O2● formation. Thus, in presence of DNBs, resting-state CaM-deficient nNOS efficiently transfers electrons generating O2
●, inferring that additional metabolic roles for nNOS exist that are not yet explored. | en_US |
Sponsorship | The authors thank Drs. Robert Kirken (UTEP) and Shaquria Adderley (ECU) for
their help in preparation of this manuscript. This work was supported by
a National Institutes of Health National Centre for Research Resources grant to
the Border Biomedical Research Center/University of Texas at El Paso
[5G12RR008124], a NIH NIEHS grant [ES011982], and by American Recovery
and Reinvestment Act Awards from the NIH National Heart, Lung, and Blood
Institute [R01HL081720; R01HL081720-03S2]. | en_US |
Language | en_US | en_US |
Related URI | http://dx.doi.org/10.7439%2Fijbr.v2i9.165 | en_US |
Subject | NNOS | en_US |
Subject | Superoxides | en_US |
Subject | NADPH | en_US |
Subject | Redox | en_US |
Title | DINITROBENZENES STIMULATE ELECTRON FLUX WITHIN NEURONAL NITRIC OXIDE SYNTHASE IN THE ABSENCE OF CALMODULIN | en_US |
Type | Article | |
Identifier (DOI) | 10.7439%2Fijbr.v2i9.165 | |
Journal Name | International Journal of Biomedical Research | |
Journal Volume | 2 | |
Journal Issue | 9 | |
Article Pages | 499-507 | |