CORO1A regulates lipoprotein uptake in Leydig cells exposed to cadmium.
CORO1A regulates lipoprotein uptake in Leydig cells exposed to cadmium.
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DOI：
10.1016/j.ecoenv.2022.113255
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发表时间：
2022-01
影响因子：
6.8
通讯作者：
Youjin Wang;Teng Li;Haojie Li;Yuqing Liang;Wanwen Mai;Chen Liu;Hongxia Chen;Yadong Huang;Qi‐hao Zhang
中科院分区：
文献类型：
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作者：
Youjin Wang;Teng Li;Haojie Li;Yuqing Liang;Wanwen Mai;Chen Liu;Hongxia Chen;Yadong Huang;Qi‐hao Zhang
镉（Cd）是最常见的环境污染物之一，具有较长的生物半衰期。母亲在自然环境中接触镉会导致类固醇生成缺陷，从而导致雄性后代的精子生成障碍。为了更好地理解其潜在机制，我们采用iTRAQ筛选差异表达蛋白，发现在镉暴露子代母体Leydig细胞中CORO1A和Cofilin 1的表达上调约2倍。胆固醇作为类固醇激素的主要来源，通过受体介导的内吞作用（依赖于细胞骨架的重塑）转运至细胞，然后储存在脂滴（LD）中。然而，很少有研究关注细胞骨架在异常类固醇生成中的作用。本研究旨在探讨 CORO1A 在 Cd 暴露引起的雄激素缺乏中的作用及其对低密度脂蛋白 (LDL) 摄取的参与以及对 LD 的影响。我们发现，母体暴露的雄性后代的睾丸中，Cd 导致 CORO1A 和 Cofilin 1 上调，Profilin 1 下调。在Cd处理的R2C细胞中，丝状肌动蛋白的结构被破坏、紊乱甚至皱缩。 F-肌动蛋白解体导致低密度脂蛋白 (LDL) 摄取量降低，同时 LD 数量减少，随后总胆固醇降低，黄体酮产生量降低。当 CORO1A 被沉默时，Cd 处理的 R2C 细胞中 Cofilin 1 的表达下调，Profilin 1 的表达上调。丝状肌动蛋白被拯救，整合的细胞骨架促进低密度脂蛋白的摄取，从而导致总胆固醇增加和黄体酮产生增加。这些发现强调了 CORO1A 作为细胞骨架调节蛋白在类固醇生成中的关键作用，这可能有助于更好地了解镉诱导的儿童类固醇激素缺乏症。
Cadmium (Cd) is one of the most common environmental pollutants, which has a long biological half-life. Maternal Cd-exposure in the natural environment causes steroidogenesis defects resulting in spermatogenesis disorder in male offspring. For better understanding its underlying mechanism, we have employed iTRAQ to screen the differentially expressed protein and found that the expression of CORO1A and Cofilin 1 was up-regulated approximately 2 fold in Leydig cells of maternal Cd-exposure offspring. As the major source of steroid hormone, cholesterol is transported to cellsviareceptor-mediated endocytosis which relies on the remodel of cytoskeleton, then stores in lipid droplets (LDs). However, few studies have focused on the role of cytoskeleton in abnormal steroidogenesis. This study was performed to explore the role of CORO1A in androgen deficiency caused by Cd exposure and its involvement of low-density lipoprotein (LDL) uptake and effects on LDs. We found that Cd resulted in the up-regulation of CORO1A and Cofilin 1, and down-regulation of Profilin 1 in the testis of male offspring with maternal exposure. The structure of filamentous actin was broken, disordered and even crumpled up in Cd-treated R2C cells. F-actin disassembly led to a low uptake of LDL with a reduced number of LDs, followed by decreased total cholesterol and low progesterone production. When CORO1A was silenced, the expression of Cofilin 1 was down-regulated and Profilin 1 was up-regulated in Cd-treated R2C cells. The filamentous actin was rescued and the integrated cytoskeleton prompted LDL uptake, which resulted in the increased total cholesterol and high progesterone production. These findings highlight the crucial role of CORO1A as a cytoskeleton regulatory protein in steroidogenesis, which may help to better understand Cd-induced steroid hormone deficiency in children.