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草甘膦暴露诱导人前列腺 PNT1A 细胞的细胞毒性、线粒体功能障碍和 ERα 和 ERβ 雌激素受体的激活。

Glyphosate Exposure Induces Cytotoxicity, Mitochondrial Dysfunction and Activation of ERα and ERβ Estrogen Receptors in Human Prostate PNT1A Cells.

机构信息

Department of Biology, University Federico II, Via Cintia 21, 80126 Napoli, Italy.

National Institute of Biostructures and Biosystems (INBB), Viale delle Medaglie d'Oro 305, 00136 Roma, Italy.

出版信息

Int J Mol Sci. 2024 Jun 27;25(13):7039. doi: 10.3390/ijms25137039.

Abstract

Glyphosate, the active ingredient of several broad-spectrum herbicides, is widely used throughout the world, although many adverse effects are known. Among these, it has been recognized as an endocrine disruptor. This work aimed to test the effects and potential endocrine disrupting action of glyphosate on PNT1A human prostate cells, an immortalized non-tumor epithelial cell line, possessing both ERα and ERβ estrogen receptors. The results showed that glyphosate induces cytotoxicity, mitochondrial dysfunction, and rapid activation of ERα and ERβ via nuclear translocation. Molecular analysis indicated a possible involvement of apoptosis in glyphosate-induced cytotoxicology. The apoptotic process could be attributed to alterations in mitochondrial metabolism; therefore, the main parameters of mitochondrial functionality were investigated using the Seahorse analyzer. Impaired mitochondrial function was observed in glyphosate-treated cells, with reductions in ATP production, spare respiratory capacity, and proton leakage, along with increased efficiency of mitochondrial coupling. Finally, the results of immunofluorescence analysis demonstrated that glyphosate acts as an estrogen disruptor determining the nuclear translocation of both ERs. Nuclear translocation occurred independent of dose, faster than the specific hormone, and persisted throughout treatment. In conclusion, the results collected show that in non-tumor prostate cells glyphosate can cause cell death and acts as a xenoestrogen, activating estrogen receptors. The consequent alteration of hormonal functions can have negative effects on the reproductive health of exposed animals, compromising their fertility.

摘要

草甘膦是几种广谱除草剂的有效成分,在全世界广泛使用,尽管已知其存在许多不良影响。其中,它已被确认为一种内分泌干扰物。本研究旨在测试草甘膦对 PNT1A 人前列腺细胞(一种具有 ERα 和 ERβ 雌激素受体的永生化非肿瘤上皮细胞系)的作用和潜在内分泌干扰作用。结果表明,草甘膦诱导细胞毒性、线粒体功能障碍,并通过核转位快速激活 ERα 和 ERβ。分子分析表明,草甘膦诱导细胞毒性作用可能涉及细胞凋亡。凋亡过程可能归因于线粒体代谢的改变;因此,使用 Seahorse 分析仪研究了线粒体功能的主要参数。在草甘膦处理的细胞中观察到线粒体功能受损,表现为 ATP 产生、备用呼吸能力和质子泄漏减少,以及线粒体偶联效率增加。最后,免疫荧光分析的结果表明,草甘膦作为一种雌激素干扰物,可导致两种 ER 的核转位。核转位发生与剂量无关,比特异性激素更快,并且在整个治疗过程中持续存在。总之,所收集的结果表明,在非肿瘤前列腺细胞中,草甘膦可导致细胞死亡,并作为一种外源性雌激素,激活雌激素受体。激素功能的改变可能对暴露于草甘膦的动物的生殖健康产生负面影响,损害其生育能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34a1/11241661/02d89af60b11/ijms-25-07039-g008.jpg

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