Gutenberg Open Science: Decoding the substrate supply to human neuronal nitric oxide synthase

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7345

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DC Field	Value	Language
dc.contributor.author	Simon, Alexandra	-
dc.contributor.author	Karbach, Susanne	-
dc.contributor.author	Habermeier, Alice	-
dc.contributor.author	Closs, Ellen I.	-
dc.date.accessioned	2022-07-11T10:04:47Z	-
dc.date.available	2022-07-11T10:04:47Z	-
dc.date.issued	2013	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7359	-
dc.description.abstract	Nitric oxide, produced by the neuronal nitric oxide synthase (nNOS) from L-arginine is an important second messenger molecule in the central nervous system: It influences the synthesis and release of neurotransmitters and plays an important role in long-term potentiation, long-term depression and neuroendocrine secretion. However, under certain pathological conditions such as Alzheimer's or Parkinson's disease, stroke and multiple sclerosis, excessive NO production can lead to tissue damage. It is thus desirable to control NO production in these situations. So far, little is known about the substrate supply to human nNOS as a determinant of its activity. Measuring bioactive NO via cGMP formation in reporter cells, we demonstrate here that nNOS in both, human A673 neuroepithelioma and TGW-nu-I neuroblastoma cells can be fast and efficiently nourished by extracellular arginine that enters the cells via membrane transporters (pool I that is freely exchangeable with the extracellular space). When this pool was depleted, NO synthesis was partially sustained by intracellular arginine sources not freely exchangeable with the extracellular space (pool II). Protein breakdown made up by far the largest part of pool II in both cell types. In contrast, citrulline to arginine conversion maintained NO synthesis only in TGW-nu-I neuroblastoma, but not A673 neuroepithelioma cells. Histidine mimicked the effect of protease inhibitors causing an almost complete nNOS inhibition in cells incubated additionally in lysine that depletes the exchangeable arginine pool. Our results identify new ways to modulate nNOS activity by modifying its substrate supply.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/3.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Decoding the substrate supply to human neuronal nitric oxide synthase	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7345	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	PLoS one	de
jgu.journal.volume	8	de
jgu.journal.issue	7	de
jgu.pages.alternative	e67707	de
jgu.publisher.year	2013	-
jgu.publisher.name	PLoS	de
jgu.publisher.place	Lawrence, Kan.	de
jgu.publisher.uri	http://dx.doi.org/10.1371/journal.pone.0067707	de
jgu.publisher.issn	1932-6203	de
jgu.organisation.place	Mainz	-
jgu.identifier.pmid	23874440	-
jgu.subject.ddccode	610	de
opus.date.modified	2018-08-02T09:33:11Z	-
opus.subject.dfgcode	00-000	-
opus.organisation.string	FB 04: Medizin: Institut für Pharmakologie	de_DE
opus.identifier.opusid	24655	-
opus.importsource	pubmed	-
opus.institute.number	0413	-
opus.metadataonly	false	-
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Karbach, Susanne	-
opus.affiliated	Closs, Ellen I.	-
jgu.publisher.doi	10.1371/journal.pone.0067707	de
jgu.organisation.ror	https://ror.org/023b0x485
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

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