Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes.
Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes.
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黄芪甲苷 IV 通过调节小鼠足细胞钙稳态抑制棕榈酸诱导的细胞凋亡
DOI：
10.1007/s11033-021-06204-4
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发表时间：
2021-03
影响因子：
2.8
通讯作者：
Peng W
中科院分区：
文献类型：
--
作者：
Zang Y;Liu S;Cao A;Shan X;Deng W;Li Z;Wang H;Wang Y;Wang L;Peng W
足细胞丢失是糖尿病肾病的标志，越来越多的证据表明足细胞对棕榈酸（PA）敏感。我们以前的研究表明，AS-IV通过激活肌内质网Ca ~（2+）ATP酶（SERCA）抑制PA诱导的足细胞凋亡，这表明钙调节可能参与了这一过程。免疫荧光染色、Western blot和流式细胞术检测AS-Ⅳ对PA诱导的ER应激和足细胞凋亡的保护作用。同时，AS-IV抑制细胞色素c的释放，降低线粒体膜电位，同时伴有内质网Ca ~（2+）的耗竭和胞浆及线粒体Ca ~（2+）的升高。BAPTA-AM对细胞内钙的螯合作用抑制足细胞凋亡，而AS-IV的作用也受到抑制。与此相反，钙离子载体离子霉素的胞浆钙升高被AS-IV抑制。此外，用SKF 96365或TRPC 6 siRNA抑制TRPC 6表达抵消了AS-IV的有益作用。本研究进一步证明了AS-IV对足细胞凋亡的抑制作用是钙依赖性的。其作用机制与抑制TRPC 6介导的Ca 2+内流，进而协调细胞内Ca 2+紊乱有关。
Loss of podocytes is a hallmark of diabetic nephropathy, and a growing body of evidence indicates that podocytes are susceptible to palmitic acid (PA). We have previously shown that AS-IV inhibited PA-induced podocyte apoptosis by activating sarcoendoplasmic reticulum Ca2+ATPase (SERCA), which indicate calcium regulation may involve in the process. Immunofluorescence staining, Western blot and flow cytometry were used to measure the protective efficacy of AS-IV to ameliorate PA-induced ER stress and podocyte apoptosis. Meanwhile, AS-IV inhibited cytochrome c release, decreased mitochondrial membrane potential, accompany with the depletion of endoplasmic reticulum Ca2+and elevation of cytosolic and mitochondrial Ca2+. Sequestration of cytosolic calcium with BAPTA-AM limited the response of podocyte apoptosis, while during the process the effect of AS-IV was also restrained. In contrast, elevation of cytosolic calcium with calcium ionophore ionomycin was depressed by AS-IV addition. Furthermore, inhibiting TRPC6 expression with SKF96365 or TRPC6 siRNA counteracted the beneficial effect of AS-IV. Our study provides further evidence to conclude the inhibitory effect of AS-IV to podocyte apoptosis is Ca2+-dependent. And the efficacy correlates with inhibiting TRPC6-mediated Ca2+influx, and then cellular Ca2+disturbance was coordinated.
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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