Sodium Selenite inhibits mitophagy, downregulation and mislocalization of blood-testis barrier proteins of bovine Sertoli cell exposed to microcystin-leucine arginine (MC-LR) via TLR4/NF-kB and mitochondrial signaling pathways blockage

亚硒酸钠通过阻断 TLR4/NF-kB 和线粒体信号通路抑制暴露于微囊藻毒素-亮氨酸精氨酸 (MC-LR) 的牛塞托利细胞的线粒体自噬、血睾屏障蛋白的下调和错误定位

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作者:E O Adegoke, Wang Xue, N S Machebe, S O Adeniran, Wang Hao, Wang Chen, Zhang Han, Zhang Guixue, Zheng Peng

Abstract

This study was conducted to investigate the ameliorative effect of selenium on microcystin-LR induced toxicity in bovine Sertoli cells. Bovine Sertoli cells were pretreated with selenium (Na2SeO3) for 24 h after which selenium pretreated and non-pretreated Sertoli cells were cultured in medium containing 10% heat activated fetal bovine serum FBS+ 80 µg/L MC-LR to assess its ameliorative effect on MC-LR toxicity. The results show that selenium pretreatment inhibited the MC-LR induced mitophagy, downregulation and mislocalization of blood-testis barrier constituent proteins in bovine Sertoli cells via NF-kB and cytochrome c release blockage. The observed downregulation of electron transport chain (ETC) related genes (mt-ND2, COX-1, COX-2) and upregulation of inflammatory cytokines (IL-6, TNF-α, IL-1β, IFN-γ, IL-4, IL-10, 1 L-13, TGFβ1) in non-pretreated cells exposed to MC-LR were ameliorated in selenium pretreated cells. There was no significant difference (P > 0.05) in the protein levels of blood-testis barrier constituent proteins (ZO-1, occludin, connexin-43, CTNNB1, N-cadherin) and mitochondria related genes (mt-ND2, COX-1, COX-2, ACAT1, mtTFA) of selenium pretreated Sertoli cell compared to the control. Taken together, we conclude that selenium inhibits MC-LR caused Mitophagy, downregulation and mislocalization of blood-testis barrier proteins of bovine Sertoli cell via mitochondrial and TLR4/NF-kB signaling pathways blockage.

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