title: LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death.
abstract: Redox status changes exert critical impacts on necrotic/apoptotic and normal cellular processes. We report here a widely expressed Ca2+-permeable cation channel, LTRPC2, activated by micromolar levels of H2O2 and agents that produce reactive oxygen/nitrogen species. This sensitivity of LTRPC2 to redox state modifiers was attributable to an agonistic binding of nicotinamide adenine dinucleotide (beta-NAD+) to the MutT motif. Arachidonic acid and Ca2+ were important positive regulators for LTRPC2. Heterologous LTRPC2 expression conferred susceptibility to death on HEK cells. Antisense oligonucleotide experiments revealed physiological involvement of "native" LTRPC2 in H2O2- and TNFalpha-induced Ca2+ influx and cell death. Thus, LTRPC2 represents an important intrinsic mechanism that mediates Ca2+ and Na+ overload in response to disturbance of redox state in cell death.
authors.affiliation: Center for Integrative Bioscience, The Graduate University for Advanced Studies, 444-8585, Okazaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hara
authors.forename: Minoru
authors.initials: M
authors.lastname: Wakamori
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.forename: Emi
authors.initials: E
authors.lastname: Maeno
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nishida
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Yamada
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Emiko
authors.initials: E
authors.lastname: Mori
authors.forename: Jun
authors.initials: J
authors.lastname: Kudoh
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurose
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okada
authors.forename: Keiji
authors.initials: K
authors.lastname: Imoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D050053:TRPM Cation Channels; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium