Epigenetic modification of H3K4 and oxidative stress are involved in MC‐LR‐induced apoptosis in testicular cells of SD rats

Yuan, Long; Liu, Haohao; Liu, Xiaohui; Zhang, Xiaofeng; Wu, Jinxia; Wang, Yueqin; Du, Xingde; Wang, Rui; Ma, Yu; Chen, Xinghai; Petlulu, Pavankumar; Cheng, Xuemin; Zhuang, Donggang; Guo, Haipeng; Zhang, Huizhen

doi:10.1002/tox.22865

Cited by 20 publications

(6 citation statements)

References 55 publications

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“…In the present study, we evaluated the expression of markers for the two enzymes lysine demethylase, responsible for the removal of methyl radicals from the H3, KDM3A, and KDM1AX1. The KDM3A decreases gene silencing, including those related to the inhibition of primordial follicle activation and the induction of apoptosis ( 43 – 45 ). The relative mRNA expression levels for KDM3A and KDM1AX1 were increased in anethole and EUG 40 treatments when compared to the non-cultured control.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we suggest that the higher rates of follicle survival and activation observed in the EUG 40 may be explained by the silencing of pro-apoptotic genes as well as genes related to the maintenance of primordial follicle quiescence. To date, studies have shown that decreased H3K4me3 levels lead to a reduction in the expression levels of pro-apoptotic genes [Bax, Bad and Bid ( 44 , 45 )].…”

Section: Discussionmentioning

confidence: 99%

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Eugenol Improves Follicular Survival and Development During in vitro Culture of Goat Ovarian Tissue

et al. 2022

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This study evaluated the effects of different concentrations (10, 20, or 40 μM) of eugenol (EUG 10, EUG 20, or EUG 40), ascorbic acid (50 μg/mL; AA) or anethole (300 μg/mL; ANE 300) on the in-vitro survival and development of goat preantral follicles and oxidative stress in the cultured ovarian tissue. Ovarian fragments from five goats were cultured for 1 or 7 days in Alpha Minimum Essential Medium (α-MEM+) supplemented or not with AA, ANE 300, EUG 10, EUG 20 or EUG 40. On day 7 of culture, when compared to MEM, the addition of EUG 40 had increased the rate of follicular development, as observed by a decrease in the proportion of primordial follicles alongside with an increase in the rate of normally developing follicles. Furthermore, EUG 40 significantly increased both follicular and oocyte diameters. Subsequently, ovarian fragments from three goats were cultured for 1 or 7 days in α-MEM+ supplemented or not with AA, ANE 300 or EUG 40. All tested antioxidants, except ANE 300, were able to significantly decrease the levels of reactive oxygen species in the ovarian tissue, but EUG 40 could most efficiently neutralize free radicals. All ovarian tissues cultured in the presence of antioxidants, especially EUG 40, presented a significant decrease in H3K4me3 labeling, indicating a silencing of genes that play a role in the inhibition of follicular activation and apoptosis induction. When compared to cultured control tissues, both EUG 40 and ANE 300 significantly increased the intensity of calreticulin labeling in growing follicles. The mRNA relative expression of ERP29 and KDM3A was significantly increased when the culture medium was supplemented with EUG 40, indicating a response to ER stress experienced during culture. In conclusion, EUG 40 improved in-vitro follicle survival, activation and development and decreased ROS production, ER stress and histone lysine methylation in goat ovarian tissue.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Eugenol Improves Follicular Survival and Development During in vitro Culture of Goat Ovarian Tissue

et al. 2022

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“…Hepatocyte apoptosis occurs in the pathological process of various liver diseases. Meanwhile, apoptosis is the most common injury caused by MC‐LR 44–46 . Bcl‐2 family members may regulate apoptosis by influencing the permeability of mitochondrial outer membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, apoptosis is the most common injury caused by MC-LR. [44][45][46] Bcl-2 family members may regulate apoptosis by influencing the permeability of mitochondrial outer membrane.…”

Section: Discussionmentioning

confidence: 99%

Hawthorn fruit extract protect against MC‐LR‐induced hepatotoxicity by attenuating oxidative stress and apoptosis

Wang

Guo

Liu

et al. 2023

Environmental Toxicology

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Microcystins (MCs) is a class of cyclic heptapeptide compounds with biological activity. There is no effective treatment for liver injury caused by MCs. Hawthorn is a medicinal and edible plant traditional Chinese medicine with hypolipidemic, reducing inflammation and oxidative stress in the liver. This study discussed the protective effect of hawthorn fruit extract (HFE) on liver damage caused by MC‐LR and the underlying molecular mechanism. After MC‐LR exposure, pathological changes were observed and hepatic activity of ALT, AST and ALP were increased obviously, but they were remarkably restored with HFE administration. In addition, MC‐LR could significantly reduce SOD activity and increase MDA content. Importantly, MC‐LR treatment resulted in mitochondrial membrane potential decreased, and Cytochrome C release, eventually leading to cell apoptosis rate increase. HFE pretreatment could significantly alleviate the above abnormal phenomena. To examine the mechanism of protection, the expression of critical molecules in the mitochondrial apoptosis pathway was examined. The levels of Bcl‐2 was inhibited, and the levels of Bax, Caspase‐9, Cleaved Caspase‐9, and Cleaved caspase‐3 were upregulated after MC‐LR treatment. HFE reduced MC‐LR‐induced apoptosis via reversing the expression of key proteins and genes in the mitochondrial apoptotic pathway. Hence, HFE could alleviate MC‐LR induced hepatotoxicity by reducing oxidative stress and apoptosis.

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“…Some speci c compounds have been found that might in uence the level of epigenetic modi cation (Liu et al, 2020a). For example, 5-deoxy5methylthiosine (MTA) is a speci c inhibitor of H3K4 methylation, which mainly inhibits H3K4 methylation, especially trimethylation (Yuan et al, 2019). Methylated histones are recognized by chromatin effectors, which recruit other molecules to alter chromatin structure and function (Taverna et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Preliminary analysis of H3K4me3 in the gonads during gonadal differentiation in the olive flounder Paralichthys olivaceus

Liu

Wang

Zou

et al. 2022

Preprint

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Histone methylation is one of the most important epigenetic modifications. However, there are few studies on its role in fish gonadal differentiation. In this study, we analyzed the patterns of H3K4me3 and the expression of modifying- and de-modifying enzymes in the gonads of the juvenile olive flounder Paralichthys olivaceus during the gonadal differentiation process. Histological analysis showed that phenotypic female or male flounder were obtained by treatment with 17β-estradiol (E2) or testosterone (T), respectively. Real-time quantitative PCR (qPCR) results presented that the expression of kmt2b at 2 and 6 cm total length (TL) was higher in the T group than in the E2 group. The expression of kdm5a and kdm5c was higher in the E2 group at 10 cm TL. The results of in situ hybridization (ISH) indicated that kmt2b was mainly distributed in oocytes of the ovary at 10 cm TL. Western blot analysis showed that, H3K4me3 levels were higher in the T group than in the E2 group at 2 and 6 cm TL. As shown with Immunohistochemistry analysis, H3K4me3 was mainly located in oocytes in the ovaries. The signal in spermatogonia was weak in the testes at 10 cm TL. After incubation with an H3K4 methylase inhibitor (5’-deoxy-5’-methylthioadenosine, MTA), the levels of H3K4me3 in the gonads were significantly decreased. The qPCR results indicated that in the MTA group, the expression of sox9a and dmrt1 was significantly decreased in the testis. These results provide the basic data that H3K4me3 may be involved in fish gonadal differentiation.

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Epigenetic modification of H3K4 and oxidative stress are involved in MC‐LR‐induced apoptosis in testicular cells of SD rats

Cited by 20 publications

References 55 publications

Eugenol Improves Follicular Survival and Development During in vitro Culture of Goat Ovarian Tissue

Eugenol Improves Follicular Survival and Development During in vitro Culture of Goat Ovarian Tissue

Hawthorn fruit extract protect against MC‐LR‐induced hepatotoxicity by attenuating oxidative stress and apoptosis

Preliminary analysis of H3K4me3 in the gonads during gonadal differentiation in the olive flounder Paralichthys olivaceus

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