Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through ROR alph

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论文题目:	Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through ROR alpha in cumulus cells of prepubertal lambs
英文论文题目:	Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through ROR alpha in cumulus cells of prepubertal lambs
第一作者:	房义
英文第一作者:	Fa Yi
联系作者:	钟荣珍
英文联系作者:	Rong Z.Zhong
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发表年度:	2019
卷:	131
期:
页码:	173-183
摘要:	Physical damage andoxidative stressmay occur in prepubertalcumulus cells, due to insufficientglutathione synthesis. To determine potentialepigenetic mechanismsrelated to antioxidant effects ofmelatoninon ovine prepubertal cumulus cells, 30 lambs, 4-wk-old were randomly allocated into two groups: a control (C, n？=？20) group and a melatonin (M, n？=？10) group given a subcutaneous implant containing 18？mg melatonin. All lambs were superovulated (250 IU FSH and 250 IU eCG). Cumulus cells fromgerminal vesiclestage cumulusoocytecomplexes (COCs) were collected by ovarianfollicular aspirationand dissociated withhyaluronidase. Compared to the C group, the M group had greatersuperovulation, betterantioxidant capacity, a higher proportion of fully expanded COCs and a lower proportion of apoptotic cumulus cells (P？<？0.05). Melatonin up-regulatedmRNAexpression of genes formelatonin receptorsMT1and nuclear binding siteRORα, antioxidants (SOD1,GPx4andCAT) and cumulus cell expansion (PTX3,HAS2andPTGS2), as well asBcl2, but down-regulated expression ofBax(P？<？0.05). Regardingepigenetics, there were lessmethylationat fiveCpG sitesofSOD1, three CpG sites ofGPx4and two CpG sites ofCATin MversusC groups (P？<？0.05), leading to lower total methylation ofSOD1,GPx4andCATpromoters region on M group (P？<？0.05). In a mechanistic study, addition of MT1 or RORα antagonist increased ROS and MDA concentrations, but decreased T-AOC, GPx, CAT and T-SOD concentrations (P？<？0.05), whereas there were no significant difference between the melatonin and MT2 antagonist treatment groups for T-AOC, GPx, CAT and T-SOD concentrations. Furthermore, addition of RORαagonistdecreased totalDNA methylationofSOD1,GPx4andCAT, with no significant difference after MT1 agonist treatment. These studies provided new information regarding epigenetic mechanisms by which melatonin promoted ovine prepubertal cumulus cells antioxidant through RORα, bothin vitroandin vivo.
英文摘要:	Physical damage andoxidative stressmay occur in prepubertalcumulus cells, due to insufficientglutathione synthesis. To determine potentialepigenetic mechanismsrelated to antioxidant effects ofmelatoninon ovine prepubertal cumulus cells, 30 lambs, 4-wk-old were randomly allocated into two groups: a control (C, n？=？20) group and a melatonin (M, n？=？10) group given a subcutaneous implant containing 18？mg melatonin. All lambs were superovulated (250 IU FSH and 250 IU eCG). Cumulus cells fromgerminal vesiclestage cumulusoocytecomplexes (COCs) were collected by ovarianfollicular aspirationand dissociated withhyaluronidase. Compared to the C group, the M group had greatersuperovulation, betterantioxidant capacity, a higher proportion of fully expanded COCs and a lower proportion of apoptotic cumulus cells (P？<？0.05). Melatonin up-regulatedmRNAexpression of genes formelatonin receptorsMT1and nuclear binding siteRORα, antioxidants (SOD1,GPx4andCAT) and cumulus cell expansion (PTX3,HAS2andPTGS2), as well asBcl2, but down-regulated expression ofBax(P？<？0.05). Regardingepigenetics, there were lessmethylationat fiveCpG sitesofSOD1, three CpG sites ofGPx4and two CpG sites ofCATin MversusC groups (P？<？0.05), leading to lower total methylation ofSOD1,GPx4andCATpromoters region on M group (P？<？0.05). In a mechanistic study, addition of MT1 or RORα antagonist increased ROS and MDA concentrations, but decreased T-AOC, GPx, CAT and T-SOD concentrations (P？<？0.05), whereas there were no significant difference between the melatonin and MT2 antagonist treatment groups for T-AOC, GPx, CAT and T-SOD concentrations. Furthermore, addition of RORαagonistdecreased totalDNA methylationofSOD1,GPx4andCAT, with no significant difference after MT1 agonist treatment. These studies provided new information regarding epigenetic mechanisms by which melatonin promoted ovine prepubertal cumulus cells antioxidant through RORα, bothin vitroandin vivo.
刊物名称:	Free Radical Biology and Medicine
英文刊物名称:	Free Radical Biology and Medicine
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参与作者:	Y. Fang, J. L. Zhang, Y. H. Li, X. F. Guo, J. J. Li, R. Z. Zhong and X. S. Zhang
英文参与作者:	Y. Fang, J. L. Zhang, Y. H. Li, X. F. Guo, J. J. Li, R. Z. Zhong and X. S. Zhang

Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through ROR alph

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