Faouzi Malika, Penner Reinhold
Center for Biomedical Research, The Queen's Medical Center, 1301 Punchbowl Street, Honolulu, HI, 96813, USA,
Handb Exp Pharmacol. 2014;222:403-26. doi: 10.1007/978-3-642-54215-2_16.
TRPM2 is the second member of the transient receptor potential melastatin-related (TRPM) family of cation channels. The protein is widely expressed including in the brain, immune system, endocrine cells, and endothelia. It embodies both ion channel functionality and enzymatic ADP-ribose (ADPr) hydrolase activity. TRPM2 is a Ca(2+)-permeable nonselective cation channel embedded in the plasma membrane and/or lysosomal compartments that is primarily activated in a synergistic fashion by intracellular ADP-ribose (ADPr) and Ca(2+). It is also activated by reactive oxygen and nitrogen species (ROS/NOS) and enhanced by additional factors, such as cyclic ADPr and NAADP, while inhibited by permeating protons (acidic pH) and adenosine monophosphate (AMP). Activation of TRPM2 leads to increases in intracellular Ca(2+) levels, which can serve signaling roles in inflammatory and secretory cells through release of vesicular mediators (e.g., cytokines, neurotransmitters, insulin) and in extreme cases can induce apoptotic and necrotic cell death under oxidative stress.
瞬时受体电位褪黑素相关（TRPM）阳离子通道家族的第二个成员是TRPM2。该蛋白广泛表达，包括在大脑、免疫系统、内分泌细胞和内皮细胞中。它兼具离子通道功能和酶促ADP-核糖（ADPr）水解酶活性。TRPM2是一种嵌入质膜和/或溶酶体区室的Ca(2+)通透非选择性阳离子通道，主要通过细胞内ADP-核糖（ADPr）和Ca(2+)以协同方式激活。它也被活性氧和氮物种（ROS/NOS）激活，并被其他因素增强，如环ADPr和NAADP，而被渗透质子（酸性pH）和单磷酸腺苷（AMP）抑制。TRPM2的激活导致细胞内Ca(2+)水平升高，这可通过释放囊泡介质（如细胞因子、神经递质、胰岛素）在炎症和分泌细胞中发挥信号作用，在极端情况下，在氧化应激下可诱导凋亡和坏死性细胞死亡。
