LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death.
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.
Hara
Yuji
Y
Center for Integrative Bioscience, The Graduate University for Advanced Studies, 444-8585, Okazaki, Japan.
Wakamori
Minoru
M
Ishii
Masakazu
M
Maeno
Emi
E
Nishida
Motohiro
M
Yoshida
Takashi
T
Yamada
Hisanobu
H
Shimizu
Shunichi
S
Mori
Emiko
E
Kudoh
Jun
J
Shimizu
Nobuyoshi
N
Kurose
Hitoshi
H
Okada
Yasunobu
Y
Imoto
Keiji
K
Mori
Yasuo
Y
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
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