51. Epigenetic modification of H3K4 and oxidative stress are involved in MC‐LR‐induced apoptosis in testicular cells of SD rats
- Author
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Pavankumar Petlulu, Huizhen Zhang, Ya Ma, Le Yuan, Xingde Du, Xuemin Cheng, Xinghai Chen, Yueqin Wang, Rui Wang, Donggang Zhuang, Haohao Liu, Xiaofeng Zhang, Hongxiang Guo, Xiaohui Liu, and Jinxia Wu
- Subjects
Male ,medicine.medical_specialty ,Microcystins ,Arginine ,Health, Toxicology and Mutagenesis ,Apoptosis ,010501 environmental sciences ,Management, Monitoring, Policy and Law ,Mitochondrion ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Epigenesis, Genetic ,Histones ,Rats, Sprague-Dawley ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Internal medicine ,Testis ,medicine ,Animals ,Humans ,0105 earth and related environmental sciences ,Membrane Potential, Mitochondrial ,chemistry.chemical_classification ,Reactive oxygen species ,Sertoli Cells ,General Medicine ,Rats ,Oxidative Stress ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,H3K4me3 ,Marine Toxins ,Reactive Oxygen Species ,Reproductive toxicity ,Oxidative stress - Abstract
Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide, produced by aquatic cyanobacteria such as microcystis, with strong reproductive toxicity which poses greater threat to the reproductive abilities of humans and animals. By exploring the role of trimethylation of histone H3 at lysine 4 (H3K4me3) and the role of oxidative stress in MC-LR-induced apoptosis in testicular Sertoli cells in Sprague-Dawley (SD) rats, this study indicated that MC-LR increased the expression levels of apoptosis-related genes by raising the levels of H3K4me3. 5'-Deoxy-5'-methylthioadenosine (MTA), the inhibitor of H3K4me3, reduced apoptosis, indicating for the first time that epigenetic modification is closely related to the testicular reproductive toxicity induced by MC-LR. MC-LR also induced oxidative stress by stimulating the generation of reactive oxygen species (ROS), and subsequently triggering mitochondria-mediated apoptotic pathway by decreasing mitochondrial membrane potential and increasing the levels of Bax, Bcl-2, Caspase-3, and so on. MC-LR-induced apoptosis of testicular cells could be decreased after pretreatment with oxidative stress inhibitor N-acetyl-cysteine (NAC). Furthermore, the pathological damage to mitochondria and testes were observed in SD rats. These results show that MC-LR can induce apoptosis by raising the levels of H3K4me3, and pretreatment with MTA can ameliorate the MC-LR-induced apoptosis of cocultured cells by lowering the levels of H3K4me3. Furthermore, NAC has a protective effect on MC-LR-induced apoptosis of testicular cells in SD rats by inhibiting the oxidative stress.
- Published
- 2019