Microcystin-leucine-arginine induces apical ectoplasmic specialization disassembly
Microcystin-leucine-arginine induces apical ectoplasmic specialization disassembly
复制标题
微囊藻毒素-亮氨酸-精氨酸诱导顶端外质特化分解
DOI：
10.1016/j.chemosphere.2020.128440
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发表时间：
2021
期刊：
影响因子：
8.8
通讯作者：
Yabing Chen
中科院分区：
文献类型：
--
作者：
Dihui Xu;Jing Wang;Yuhan Ma;Jie Ding;Xiaodong Han;Yabing Chen
微囊藻毒素-亮氨酸-精氨酸(MC-LR)是一种具有肝毒性的有害物质。在本研究中，将MC-LR按1、10、20和30μg/L的剂量分别暴露于小鼠饮用水中90天和180天。我们验证了MC-LR加速了精子细胞的脱落，并在睾丸中造成了大的空泡，减少了精子数量，增加了形态异常精子的比例。此外，我们还发现MC-LR通过破坏F-肌动蛋白的组织来诱导顶端胞质特化(ES)的解体。进一步的研究发现，肌动蛋白交联蛋白Palladin的下调可能与MC-LR暴露后小鼠睾丸顶端ES的分解有关。我们还证实，MC-LR干扰了Palladin和其他肌动蛋白相关蛋白之间的相互作用，从而阻碍了F-肌动蛋白的组织。此外，我们还发现AMPK/ULK1信号通路启动的自噬介导了MC-LR攻击的Sertoli细胞中Palladin的降解。MC-LR作用后，PP2A活性降低，LKB1和CAMKK2表达上调，可激活AMPK。综上所述，这些结果表明MC-LR通过AMPK/ULK1介导的自噬诱导Palladin的降解，这可能导致顶端ES紊乱和精子细胞从生精上皮脱落。我们的工作可能为理解MC-LR诱导的男性不育提供一个新的视角。
Microcystin-leucine-arginine (MC-LR) has been identified to be a hazardous material to cause hepatotoxicity. In this study, mice were exposed to MC-LR dissolved in drinking water at doses of 1, 10, 20 and 30 μg/L for 90 and 180 days, respectively. We validated MC-LR accelerated spermatid exfoliation and caused large vacuoles in testes, reducing sperm count and increasing percentage of morphologically abnormal sperm. Furthermore, we found MC-LR induced the apical ectoplasmic specialization (ES) disassembly by disrupting F-actin organization. Further studies identified that downregulation of Palladin, the actin crosslinking protein, might be associated with disassembly of the apical ES in mice testis following MC-LR exposure. We also confirmed that MC-LR disrupted the interaction between Palladin and other actin-related proteins and thus impeded the F-actin organization. Additionally, we found that autophagy initiated by AMPK/ULK1 signaling pathway mediated the degradation of Palladin in Sertoli cells challenged with MC-LR. Following exposure to MC-LR, reduced PP2A activity and upregulated expression of LKB1 and CAMKK2 could activate AMPK. In conclusion, these results revealed MC-LR induced the degradation of Palladin via AMPK/ULK1-mediated autophagy, which might result in the apical ES disorder and spermatid exfoliation from spermatogenic epithelium. Our work may provide a new perspective to understand MC-LR-induced male infertility.