title: L-arginine is a radioprotector for hematopoietic progenitor cells.
abstract: L-arginine is shown to protect hematopoietic progenitor (32D cl 3) cells from death due to exposure to γ radiation ((137)Cs). Some of the other intermediates in the urea cycle, namely ornithine and citrulline, plus urea itself, were not found to have any significant impact on cell survival after irradiation. Intriguingly, supplementation of irradiated cells with L-arginine results in decreased production of peroxynitrite, suggesting that suppression of superoxide generation by nitric oxide synthase in one or more microenvironments is an important factor in the observed radioprotection. The absence of any radioprotective effect of L-arginine in cells at 3% oxygen also confirms the involvement of one or more oxygen-derived species. Knockdown experiments with nitric oxide synthase (NOS) siRNAs in cells and NOS knockout animals confirm that the observed radioprotection is associated with nNOS (NOS-1). L-arginine also ameliorates the transient inhibition of the electron-transport chain complex I that occurs within 30 min of completing the dose (10 Gy) and that appears to be a functional marker for postirradiation mitochondrial oxidant production.
authors.affiliation: Department of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15219-3138, USA.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Pearce
authors.forename: Xichen
authors.initials: X
authors.lastname: Zheng
authors.forename: Sandra
authors.initials: S
authors.lastname: Martinez-Bosch
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Kerr
authors.forename: Pornsri
authors.initials: P
authors.lastname: Khlangwiset
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Fink
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: Jim
authors.initials: J
authors.lastname: Peterson
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001562:Benzimidazoles / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009206:Myocardium / Q000166:cytology; D009569:Nitric Oxide / Q000096:biosynthesis; D016877:Oxidants / Q000096:biosynthesis / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001562:Benzimidazoles; D002232:Carbocyanines; D016877:Oxidants; D011837:Radiation-Protective Agents; D030421:Peroxynitrous Acid; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D009569:Nitric Oxide; D001120:Arginine; D042967:Electron Transport Complex I