P2X7 receptor-dependent and -independent T cell death is induced by nicotinamide adenine dinucleotide
P2X7 receptor-dependent and -independent T cell death is induced by nicotinamide adenine dinucleotide
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DOI：
10.4049/jimmunol.174.4.1971
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发表时间：
2005-02-15
影响因子：
4.4
通讯作者：
Dennert, G
中科院分区：
文献类型：
--
作者：
Kawamura, H;Aswad, F;Dennert, G
将 NAD 添加到小鼠 T 淋巴细胞中会抑制其功能并诱导膜联蛋白 V 结合。该报告表明，NAD 在几秒钟内诱导 T 细胞子集的细胞死亡，而其他 T 细胞直到几个小时后才会死亡。低 NAD 浓度 (100 muM) 可被 caspase 抑制剂 Z-VADfmk 阻断，与 DNA 片段化相关，并且不需要 P2X7 受体。 T 细胞将 NAD 降解为 ADP-核糖 (ADPR)，向 T 细胞添加 ADPR 会导致细胞缓慢但不快速死亡。 NAD（而非 ADPR）为 ADP-核糖基转移酶 (ART-2) 介导的 ADP-核糖基与细胞表面蛋白的附着提供底物； NAD 需要 ART-2 的表达来触发快速而非缓慢的细胞死亡。这些结果支持这样的假设：细胞表面 ART-2 使用 NAD 而不是 ADPR 将 ADP-核糖基附着到细胞表面，并且这些基团充当 P2X7 受体的配体，然后诱导快速细胞死亡。添加 NAD 或 ADPR 也会触发一组不同的机制，不需要 ART-2 或 P2X7 受体来更缓慢地诱导细胞死亡。
Adding NAD to murine T lymphocytes inhibits their functions and induces annexin V binding. This report shows that NAD induces cell death in a subset of T cells within seconds whereas others do not die until many hours later. Low NAD concentrations (100 muM), is blocked by caspase inhibitor Z-VADfmk, is associated with DNA fragmentation, and does not require P2X7 receptors. T cells degrade NAD to ADP-ribose (ADPR), and adding ADPR to T cells leads to slow but not rapid cell death. NAD but not ADPR provides the substrate for ADP-ribosyltransferase (ART- 2)-mediated attachment of ADP-ribosyl groups to cell surface proteins; expression of ART-2 is required for NAD to trigger rapid but not slow cell death. These results support the hypothesis that cell surface ART-2 uses NAD but not ADPR to attach ADP-ribosyl groups to the cell surface, and that these groups act as ligands for P2X7 receptors that then induce rapid cell death. Adding either NAD or ADPR also triggers a different set of mechanisms, not requiring ART-2 or P2X7 receptors that more slowly induce cell death.