cADP-ribose/ryanodine channel/Ca2+-release signal transduction pathway in mesangial cells.
cADP-ribose/ryanodine channel/Ca2+-release signal transduction pathway in mesangial cells.
复制标题
系膜细胞中的cADP-核糖/兰尼碱通道/Ca2-释放信号转导途径。
DOI：
10.1152/ajprenal.2001.281.1.f91
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Grande,JP
中科院分区：
文献类型：
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作者：
Yusufi,AN;Cheng,J;Thompson,MA;Dousa,TP;Warner,GM;Walker,HJ;Grande,JP
通过从细胞内储存释放Ca 2+的信号传导由几个系统介导，包括肌醇1，4，5-三磷酸（IP 3）和cADP-核糖（cADPR）途径。最近，我们发现大鼠肾小球和培养的系膜细胞（MC）的cADPR合成的高容量。我们试图确定1）MC中cADPR的合成是否受细胞因子和激素的调节，2）MC中是否表达ryanodine受体（RyRs），3）Ca 2+是否通过RyRs响应cADPR而释放。我们发现，ADP-核糖环化酶，一种催化cADPR合成的CD 38样酶，在MC中被肿瘤坏死因子-α、白细胞介素-1 β和全反式维甲酸（atRA）上调。[3 H]ryanodine以Ca 2+依赖性方式与MC微粒体组分高亲和力结合;特异性RyR激动剂可增强结合，钌红和cADPR可阻断结合。Western blot分析证实MC中存在RyR。cADPR可刺激MC微粒体释放~（45）Ca ~（2+），钌红和8-溴-cADPR可阻断释放。ADPR（非循环）无影响。在MC中，TNF-α和atRA可增强加压素引起的胞浆Ca ~（2+）升高。我们的结论是，MC具有一种新的ADP-核糖环化酶→cADPR→RyR→ Ca 2 +-释放信号通路的元件受促炎细胞因子和类固醇超家族激素的调节。
Signaling via release of Ca2+from intracellular stores is mediated by several systems, including the inositol 1,4,5-trisphosphate (IP3) and cADP-ribose (cADPR) pathway. We recently discovered a high capacity for cADPR synthesis in rat glomeruli and cultured mesangial cells (MC). We sought to determine whether1) cADPR synthesis in MC is regulated by cytokines and hormones,2) ryanodine receptors (RyRs) are expressed in MC, and3) Ca2+is released through RyRs in response to cADPR. We found that ADP-ribosyl cyclase, a CD38-like enzyme that catalyzes cADPR synthesis, is upregulated in MC by tumor necrosis factor-α, interleukin-1β, and all-transretinoic acid (atRA). [3H]ryanodine binds to microsomal fractions from MC with high affinity in a Ca2+-dependent manner; binding is enhanced by specific RyR agonists and blocked by ruthenium red and cADPR. Western blot analysis confirmed the presence of RyR in MC. Release of45Ca2+from MC microsomes was stimulated by cADPR; release was blocked by ruthenium red and 8-bromo-cADPR. ADPR (non-cyclic) was without effect. In MC, TNF-α and atRA amplified the increment of cytoplasmic Ca2+elicited by vasopressin. We conclude that MC possess elements of a novel ADP-ribosyl cyclase→cADPR→RyR→Ca2+-release signaling pathway subject to regulation by proinflammatory cytokines and steroid superfamily hormones.