LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death
LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death
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DOI：
10.1016/s1097-2765(01)00438-5
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发表时间：
2002-01-01
期刊：
影响因子：
16
通讯作者：
Mori, Y
中科院分区：
文献类型：
--
作者：
Hara, Y;Wakamori, M;Mori, Y
氧化还原状态变化对坏死/凋亡和正常细胞过程产生关键影响。我们在这里报告了一个广泛表达的呼叫渗透阳离子通道，LTRPC 2，激活微摩尔水平的过氧化氢和代理商，产生活性氧/氮物种。LTRPC 2对氧化还原状态调节剂的这种敏感性可归因于烟酰胺腺嘌呤二核苷酸（β-NAD（+））与MutT基序的激动性结合。花生四烯酸和Call是LTRPC 2的重要正调控因子。异源LTRPC 2表达赋予HEK细胞对死亡的易感性。反义寡核苷酸实验揭示了“天然”LTRPC 2在H2 O2和TNFa诱导的Ca 2+内流和细胞死亡中的生理参与。因此，LTRPC 2代表了一个重要的内在机制，介导的Ca 2+和Na+过载响应于细胞死亡中的氧化还原状态的干扰。
Redox status changes exert critical impacts on necrotic/apoptotic and normal cellular processes. We report here a widely expressed Call-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 Call 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.