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新型乙醇溶性牡蛎肽-锌螯合剂的研究进展:结构特征、螯合机制及对 MEHP 诱导的睾丸间质细胞的潜在保护作用。

Novel Insights into Ethanol-Soluble Oyster Peptide-Zinc-Chelating Agents: Structural Characterization, Chelation Mechanism, and Potential Protection on MEHP-Induced Leydig Cells.

机构信息

Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, College of Food Science and Technology, National Research and Development Branch Center for Shellfish Processing, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Ocean University, Zhanjiang 524088, China.

School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian 463000, China.

出版信息

Mar Drugs. 2024 Oct 10;22(10):465. doi: 10.3390/md22100465.

DOI:10.3390/md22100465
PMID:39452873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11509544/
Abstract

Numerous studies have reported that mono-(2-ethylhexyl) phthalate (MEHP) (bioactive metabolite of Di(2-ethylhexyl) phthalate) has inhibitory effects on Leydig cells. This study aims to prepare an oyster peptide-zinc complex (PEP-Zn) to alleviate MEHP-induced damage in Leydig cells. Zinc-binding peptides were obtained through the following processes: zinc-immobilized affinity chromatography (IMAC-Zn), liquid chromatography-mass spectrometry technology (LC-MS/MS) analysis, molecular docking, molecular dynamic simulation, and structural characterization. Then, the Zn-binding peptide (PEP) named Glu-His-Ala-Pro-Asn-His-Asp-Asn-Pro-Gly-Asp-Leu (EHAPNHDNPGDL) was identified. EHAPNHDNPGDL showed the highest zinc-chelating ability of 49.74 ± 1.44%, which was higher than that of the ethanol-soluble oyster peptides (27.50 ± 0.41%). In the EHAPNHDNPGDL-Zn complex, Asn-5, Asp-7, Asn-8, His-2, and Asp-11 played an important role in binding to the zinc ion. Additionally, EHAPNHDNPGDL-Zn was found to increase the cell viability, significantly increase the relative activity of antioxidant enzymes and testosterone content, and decrease malondialdehyde (MDA) content in MEHP-induced TM3 cells. The results also indicated that EHAPNHDNPGDL-Zn could alleviate MEHP-induced apoptosis by reducing the protein level of p53, p21, and Bax, and increasing the protein level of Bcl-2. These results indicate that the zinc-chelating peptides derived from oyster peptides could be used as a potential dietary zinc supplement.

摘要

许多研究报告称,邻苯二甲酸二(2-乙基己基)酯(MEHP)(邻苯二甲酸二(2-乙基己基)酯的生物活性代谢物)对间质细胞具有抑制作用。本研究旨在制备牡蛎肽-锌复合物(PEP-Zn)以减轻 MEHP 诱导的间质细胞损伤。通过以下过程获得锌结合肽:锌固载亲和层析(IMAC-Zn)、液相色谱-质谱联用技术(LC-MS/MS)分析、分子对接、分子动力学模拟和结构表征。然后,鉴定出锌结合肽(PEP),命名为 Glu-His-Ala-Pro-Asn-His-Asp-Asn-Pro-Gly-Asp-Leu(EHAPNHDNPGDL)。EHAPNHDNPGDL 表现出最高的锌螯合能力,为 49.74±1.44%,高于乙醇可溶牡蛎肽(27.50±0.41%)。在 EHAPNHDNPGDL-Zn 复合物中,Asn-5、Asp-7、Asn-8、His-2 和 Asp-11 在与锌离子结合中起重要作用。此外,发现 EHAPNHDNPGDL-Zn 可通过降低 p53、p21 和 Bax 的蛋白水平,增加 Bcl-2 的蛋白水平,增加 TM3 细胞中细胞活力,显著增加抗氧化酶的相对活性和睾酮含量,降低丙二醛(MDA)含量,从而减轻 MEHP 诱导的细胞凋亡。结果还表明,EHAPNHDNPGDL-Zn 可以通过降低 p53、p21 和 Bax 的蛋白水平,增加 Bcl-2 的蛋白水平,减轻 MEHP 诱导的细胞凋亡。这些结果表明,牡蛎肽衍生的锌结合肽可作为一种潜在的膳食锌补充剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/c3f7cfbfecba/marinedrugs-22-00465-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/480c3801e2a4/marinedrugs-22-00465-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/c3f7cfbfecba/marinedrugs-22-00465-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/48db85fd63b9/marinedrugs-22-00465-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/b8860aec7b2c/marinedrugs-22-00465-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/3c2794df84d6/marinedrugs-22-00465-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/480c3801e2a4/marinedrugs-22-00465-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570d/11509544/c3f7cfbfecba/marinedrugs-22-00465-g009.jpg

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