Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide -: A splice variant reveals a mode of activation independent of ADP-ribose
Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide -: A splice variant reveals a mode of activation independent of ADP-ribose
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DOI：
10.1074/jbc.m112096200
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发表时间：
2002-06-28
影响因子：
4.8
通讯作者：
Lückhoff, A
中科院分区：
文献类型：
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作者：
Wehage, E;Eisfeld, J;Lückhoff, A
LTRPC 2是最近报道的被二磷酸腺苷-核糖（ADP-核糖）和NAD激活的阳离子通道。由于ADP-核糖可以由NAD形成，并且NAD在氧化应激期间升高，我们研究了用过氧化氢（H2 O2）刺激后长瞬时受体电位通道2（LTRPC 2）转染的HEK 293细胞中的全细胞电流和细胞间游离钙浓度（[Ca 2 +]（i））的增加。一价阳离子和Ca 2+携带的阳离子电流由H2 O2（浴溶液中5 mm）以及细胞内ADP-核糖（移液管溶液中0.3 mm）诱导，但不由NAD（1 mm）诱导。H2 O2诱导的电流缓慢发展后的特征延迟3-6分钟和消退后洗出的H2 O2。[Ca2+]（i）在LTRPC 2转染细胞和对照细胞中迅速增加;然而，在LTRPC 2转染细胞中，H2 O2引起[Ca 2 +]（i）的第二次延迟升高。在嗜中性粒细胞中鉴定了在C末端（氨基酸1292-1325）具有缺失的LTRPC 2的剪接变体。该变体与野生型一样被H2 O2刺激。然而，它对ADP-核糖没有反应。我们的结论是，激活LTRPC 2的H2 O2是独立的ADP-核糖，LTRPC 2可能介导的Na+和Ca 2+的流入在氧化应激，如呼吸爆发在粒细胞。
LTRPC2 is a cation channel recently reported to be activated by adenosine diphosphate-ribose (ADP-ribose) and NAD. Since ADP-ribose can be formed from NAD and NAD is elevated during oxidative stress, we studied whole cell currents and increases in the intercellular free calcium concentration ([Ca2+](i)) in long transient receptor potential channel 2 (LTRPC2)-transfected HEK 293 cells after stimulation with hydrogen peroxide (H2O2). Cation currents carried by monovalent cations and Ca2+ were induced by H2O2 (5 mm in the bath solution) as well as by intracellular ADP-ribose (0.3 mm in the pipette solution) but not by NAD (1 mm). H2O2-induced currents developed slowly after a characteristic delay of 3-6 min and receded after wash-out of H2O2. [Ca2+](i) was rapidly increased by H2O2 in LTRPC2-transfected cells as well as in control cells; however, in LTRPC2-transfected cells, H2O2 evoked a second delayed rise in [Ca2+](i). A splice variant of LTRPC2 with a deletion in the C terminus (amino acids 1292-1325) was identified in neutrophil granulocytes. This variant was stimulated by H2O2 as the wild type. However, it did not respond to ADP-ribose. We conclude that activation of LTRPC2 by H2O2 is independent of ADP-ribose and that LTRPC2 may mediate the influx of Na+ and Ca2+ during oxidative stress, such as the respiratory burst in granulocytes.