title: Ca2+ pool emptying stimulates Ca2+ entry activated by S-nitrosylation.
abstract: The entry of Ca2+ following Ca2+ pool release is a major component of Ca2+ signals; yet despite intense study, how "store-operated" entry channels are activated is unresolved. Because S-nitrosylation has become recognized as an important regulatory modification of several key channel proteins, its role in Ca2+ entry was investigated. A novel class of lipophilic NO donors activated Ca2+ entry independent of the well defined NO target, guanylate cyclase. Strikingly similar entry of Ca2+ induced by cell permeant alkylators indicated that this Ca2+ entry process was activated through thiol modification. Significantly, Ca2+ entry activated by either NO donors or alkylators was highly stimulated by Ca2+ pool depletion, which increased both the rate of Ca2+ release and the sensitivity to thiol modifiers. The results indicate that S-nitrosylation underlies activation of an important store-operated Ca2+ entry mechanism.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Favre
authors.forename: C A
authors.initials: CA
authors.lastname: Ufret-Vincenty
authors.forename: M R
authors.initials: MR
authors.lastname: Stone
authors.forename: H T
authors.initials: HT
authors.lastname: Ma
authors.forename: D L
authors.initials: DL
authors.lastname: Gill
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D008168:Lung / Q000166:cytology; D009130:Muscle, Smooth / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000477:Alkylating Agents; D009573:Nitrites; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D014230:Triazoles; D009599:Nitroprusside; D009569:Nitric Oxide; C082874:GEA 3162; D002118:Calcium