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首页> 外文期刊>FEBS Open Bio >Estrogen inhibits starvation‐induced apoptosis in osteocytes by a redox‐independent process involving association of JNK and glutathione S‐transferase P1‐1
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Estrogen inhibits starvation‐induced apoptosis in osteocytes by a redox‐independent process involving association of JNK and glutathione S‐transferase P1‐1

机译：雌激素通过依赖于JNK和谷胱甘肽S-转移酶P1-1的氧化还原独立过程抑制饥饿诱导的骨细胞凋亡

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Estrogen deficiency causes bone loss as a result of microdamage, oxidative stress, and osteocyte apoptosis. A relationship between oxidative stress‐induced apoptosis, c‐Jun N‐terminal kinase (JNK) activation, and expression of factors involved in bone remodeling has been demonstrated in osteocytes. However, the molecular regulation of these events in osteocytes treated with 17β‐estradiol (17β‐E2) remains unexplored. The MLO‐Y4 murine osteocyte‐like cell line was used as a model to study starvation‐induced apoptosis and ROS production during 17β‐E2 treatment. Expression of glutathione S‐transferase P1‐1 (GSTP1‐1), receptor activator kB ligand (RANKL), osteoprotegerin (OPG), sclerostin, and kinases activation were measured by western blot. In addition, the GSTP1‐1/JNK association was assessed by immunoprecipitation, and GSTP1‐1 involvement in the osteocyte response to 17β‐E2 was detected by specific siRNA transfection. 17β‐E2 prevents starvation‐induced apoptosis (DNA fragmentation and caspase activation), the increase in sclerostin expression and the RANKL/OPG ratio, which are all related to JNK activation due to oxidative stress in osteocytes. This occurs through GSTP1‐1 overexpression, which can inhibit JNK activation by formation of a GSTP1‐1/JNK complex. No early antioxidant action of 17β‐E2 has been found but the estrogen effect is similar to N‐acetylcysteine which, by increasing the intracellular redox state, maintains JNK bound to GSTP1‐1. Thus, the antiapoptotic and osteogenic effect of 17β‐E2 in MLO‐Y4 occurs by a redox‐independent process involving GSTP1‐1/JNK association. This study clarifies at molecular level the effect of 17β‐E2 on osteocyte activity and identifies a possible role of GSTP1‐1 and JNK activity in bone remodeling and repair mechanisms.
机译：雌激素缺乏会由于微损伤，氧化应激和骨细胞凋亡而导致骨质流失。在骨细胞中已经证明了氧化应激诱导的细胞凋亡，c-Jun N-末端激酶（JNK）活化与参与骨重塑的因子表达之间的关系。然而，在用17β-雌二醇（17β-E2）处理的骨细胞中，这些事件的分子调控尚待探索。 MLO-Y4鼠类骨细胞样细胞系用作研究17β-E2治疗期间饥饿诱导的细胞凋亡和ROS产生的模型。通过western blot检测谷胱甘肽S转移酶P1-1（GSTP1-1），受体激活剂kB配体（RANKL），骨保护素（OPG），硬化素和激酶的表达。此外，通过免疫沉淀法评估了GSTP1-1 / JNK的关联，并通过特异性siRNA转染检测了GSTP1-1与骨细胞对17β-E2反应的关系。 17β-E2可防止饥饿诱导的细胞凋亡（DNA片段化和caspase活化），硬化素表达的增加和RANKL / OPG的比率，这些都与骨细胞氧化应激导致的JNK活化有关。这是通过GSTP1-1过表达而发生的，它可以通过形成GSTP1-1 / JNK复合体来抑制JNK激活。尚未发现17β-E2的早期抗氧化作用，但雌激素作用类似于N-乙酰半胱氨酸，后者通过增加细胞内的氧化还原状态，维持JNK与GSTP1-1的结合。因此，17β-E2在MLO-Y4中的抗凋亡和成骨作用是通过涉及GSTP1-1 / JNK关联的氧化还原独立过程而发生的。这项研究在分子水平上阐明了17β-E2对骨细胞活性的影响，并确定了GSTP1-1和JNK活性在骨重塑和修复机制中的可能作用。

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