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首页> 外文期刊>Journal of applied toxicology >Regulation of intracellular Ca by reactive oxygen species in osteoblasts treated with antimycin A
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Regulation of intracellular Ca by reactive oxygen species in osteoblasts treated with antimycin A

机译：用抗霉素A处理的成骨细胞中的反应性氧气细胞内Ca调节

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ABSTRACT: This study evaluated the effects of antimycin A (AMA), an inhibitor of electron transport in mitochondria, on the release of intracellular calcium ion ([Ca~(2+)]_i), ROS and bone resorbing factors in osteoblastic MC3T3-E1 cells. Pretreatment of osteoblasts with trolox, a ROS scavenger, and cyclosporin A, a potent inhibitor of calcium release from mitochondria, prevented the AMA-induced increases in [Ca~(2+)]_i. However, [Ca~(2+)]_i increase by AMA was unaffected by dantrolene, which blocks the ryanodine receptor channel of the endoplasmic reticulum. BAPTA/AM (an intracellular Ca~(2+) chelator), dantrolene and cyclosporine A did not reverse the effect of AMA on ROS release. We also investigated whether intracellular calcium release inhibitor and antioxidant protect against AMA-induced bone resorbing cytokine release. Trolox prevented the release of receptor activator of nuclear factor-kappaB ligand (RANKL), IL-6, and TNF-alpha induced by AMA. Moreover, the increased IL-6 and TNF-a release by AMA was markedly reduced by BAPTA/AM and cyclosporin A. However, BAPTA/AM did not reverse the effect of AMA on osteoprotegerin and RANKL. Taken together, these results demonstrate that mitochondrial ROS generation and Ca~(2+) influx by AMA is required for osteoblast death and bone resorbing cytokine release.
机译：摘要评估抗霉素A（AMA），线粒体中电子传输抑制剂对细胞内钙离子（[Ca〜（2 +）] _ I），ROS和骨吸收因子在骨晶体MC3T3中的影响 - E1细胞。用滴鼻液，ROS清除剂和环孢菌素A，从线粒体的钙释放有效抑制剂的预处理，防止了[Ca〜（2 +）] _ i的AMA诱导的增加。然而，[Ca〜（2 +）] _ I通过AMA增加未受甘油烯的影响，阻止内质网的ryanodine受体通道。 Bapta / AM（细胞内Ca〜（2+）螯合剂），甘油酮和环孢菌素A并未逆转AMA对ROS释放的影响。我们还研究了细胞内钙释放抑制剂和抗氧化剂防止A​​MA诱导的骨囊再吸收细胞因子释放。 Troolox阻止了AMA诱导的核因子-κB配体（RANKL），IL-6和TNF-α的受体激活剂的释放。此外，通过Bapta / AM和环孢菌素A显着降低了AMA的IL-6和TNF-A释放的增加。然而，Bapta / Am并未逆转AMA对骨蛋白酶和RANKL的影响。总之，这些结果表明，Osteoooblast死亡和骨头再吸收细胞因子释放需要AMA的线粒体ROS生成和Ca〜（2+）。

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