Resmethrin disrupts mitochondria-associated membranes and activates endoplasmic reticulum stress, leading to proliferation inhibition in cultured mouse Leydig and Sertoli cells
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引用次数: 0
Abstract
Resmethrin, a pyrethroid pesticide used to control insects, is toxic to non-target organisms and other mammals. However, little is known about the reproductive toxicity of resmethrin in the testes, or its mechanism of toxicity. In this study, we investigated the testicular toxicity of resmethrin on mouse Leydig (TM3) and Sertoli (TM4) cells, focusing on the mitochondria and endoplasmic reticulum (ER). We found that resmethrin inhibited proliferation and cell cycle progression and disrupted mitochondrial membrane potential (MMP; ΔΨ) in TM3 and TM4 cells. In particular, resmethrin exposure significantly reduced the expression of mitochondria-associated membranes (MAMs) proteins, such as Vapb, Vdac, and Grp75, in both cell lines. Resmethrin also disrupts calcium homeostasis in the mitochondrial matrix and cytoplasm. In addition, resmethrin activates oxidative stress-mediated ER stress signals. Finally, we confirmed that 4-PBA, an ER stress inhibitor, restored the growth of TM3 and TM4 cells, which was decreased by resmethrin. Therefore, we confirmed that resmethrin hampered MAMs and activated ER stress, thus suppressing TM3 and TM4 cell proliferation.
期刊介绍:
Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance.
Research Areas Emphasized Include the Biochemistry and Physiology of:
• Comparative toxicity
• Mode of action
• Pathophysiology
• Plant growth regulators
• Resistance
• Other effects of pesticides on both parasites and hosts.