低剂量的食品污染物脱氧雪腐镰刀菌烯醇会引发细胞凋亡并改变促性腺激素对促性腺激素细胞的刺激作用

Guodong Cai, Lingchen Yang, Francis Marien-Bourgeois, Derek Boerboom, Gustavo Zamberlam, Imourana Alassane-Kpembi
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引用次数: 0

摘要

镰刀菌霉菌毒素脱氧雪腐镰刀菌烯醇(DON)对人类和动物的健康都构成了严重威胁。它可以穿过血脑屏障,破坏大脑功能。DON 毒性的主要机制之一是激活丝裂原活化蛋白激酶(MAPKs)。促性腺激素释放激素(GnRH)刺激垂体促性腺激素细胞释放黄体生成素(LH)和卵泡刺激素(FSH)也会触发 MAPKs 通路。然而,还没有研究调查过 DON 对垂体促性腺激素的内分泌干扰作用。为了填补这一空白,我们的研究利用小鼠促性腺激素 LβT2 细胞研究了 DON 对促性腺激素细胞活力的影响,以及它对 GnRH 刺激的 FSH 和 LH 分泌的影响。我们的研究结果表明,低剂量暴露于 DON(1nM)会显著降低促性腺激素细胞在 24 小时和 48 小时内的活力。此外,DON 还能特异性抑制 GnRH 诱导的 Erk 磷酸化,而 p38 则不受影响。随后用 DON 处理过的 LβT2 细胞进行 GnRH 刺激实验,结果显示与促性腺激素释放激素受体(GnRHr)、促黄体生成素亚基 beta(LHβ)和糖蛋白激素 alpha 亚基(Cgα)相关的基因表达出现了剂量依赖性减少,同时 LH 的分泌也减少了。我们的研究结果强调了 DON 通过活性细胞凋亡诱导细胞毒性,并通过抑制 MAPKs 通路中的 Erk 磷酸化影响 LH 分泌。这项研究有助于更好地理解DON的神经毒性效应,并为进一步研究霉菌毒素对神经内分泌的影响奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Low doses of the food contaminant Deoxynivalenol trigger apoptosis and alter GnRH stimulation of gonadotroph cells
The Fusarium mycotoxin Deoxynivalenol (DON) represents a significant threat to both human and animal health. It can cross the blood-brain barrier and disrupt cerebral functions. One of the main mechanisms underlying DON toxicity involves the activation of mitogen-activated protein kinases (MAPKs). Gonadotropin-Releasing Hormone (GnRH) stimulation of pituitary gonadotroph cells to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) triggers the MAPKs pathway too. Yet, no research investigated the endocrine-disrupting effects of DON on pituitary gonadotropins. To address this gap, our study investigated the effects of DON on gonadotroph cell viability, and its impact on the GnRH-stimulated secretion of FSH and LH, using the murine gonadotroph LβT2 cells. Our results uncovered that low-dose exposure to DON (1nM) significantly impairs viability in gonadotroph cells at both 24 and 48 h. Moreover, exposure to DON shows to induce membrane phosphatidylserine translocation without loss of membrane integrity, supporting a DON-induced cytotoxicity through apoptosis initiation. Furthermore, DON specifically inhibits GnRH-induced Erk phosphorylation, while leaving p38 unaffected. Subsequent experiments with DON-treated LβT2 cells stimulated with GnRH showed a dose-dependent reduction in gene expression associated Gonadotropin-Releasing Hormone receptor (GnRHr), Luteinizing Hormone subunit beta (LHβ), and Glycoprotein Hormones, alpha subunit (Cgα), along with a reduction in LH production. Our findings underscore the induction of DON cytotoxicity through active apoptosis and its impact on LH secretion by inhibiting Erk phosphorylation within the MAPKs pathway. This research contributes to a better understanding of the neurotoxic effects of DON and establishes a foundation for further studies exploring the neuroendocrine impact of mycotoxins.
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