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

IF 4.9 2区医学 Q1 CHEMISTRY, MEDICINAL

Marine Drugs Pub Date : 2024-10-10 DOI:10.3390/md22100465

Zhen Lu, Qianqian Huang, Xiaoming Qin, Fujia Chen, Enzhong Li, Haisheng Lin

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引用次数: 0

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-Zn²⁺), 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.

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乙醇溶性牡蛎肽锌螯合剂的新见解：结构特征、螯合机理以及对 MEHP 诱导的 Leydig 细胞的潜在保护作用。

大量研究表明，邻苯二甲酸单（2-乙基己基）酯（MEHP）（邻苯二甲酸二（2-乙基己基）酯的生物活性代谢产物）对雷德氏细胞具有抑制作用。本研究旨在制备牡蛎肽锌复合物（PEP-Zn），以减轻 MEHP 对 Leydig 细胞的损伤。研究人员通过锌固定化亲和层析（IMAC-Zn2+）、液相色谱-质谱技术（LC-MS/MS）分析、分子对接、分子动力学模拟和结构表征等过程获得了锌结合肽。然后，确定了名为 Glu-His-Ala-Pro-Asn-His-Asp-Asn-Pro-Gly-Asp-Leu (EHAPNHDNPGDL) 的 Zn 结合肽（PEP）。EHAPNHDNPGDL 的锌螯合能力最高，为 49.74 ± 1.44%，高于乙醇溶性牡蛎肽（27.50 ± 0.41%）。在 EHAPNHDNPGDL-Zn 复合物中，Asn-5、Asp-7、Asn-8、His-2 和 Asp-11 在与锌离子结合方面发挥了重要作用。此外，研究还发现 EHAPNHDNPGDL-Zn 能提高 MEHP 诱导的 TM3 细胞的细胞活力，显著提高抗氧化酶的相对活性和睾酮含量，降低丙二醛（MDA）含量。研究结果还表明，EHAPNHDNPGDL-锌可通过降低 p53、p21 和 Bax 蛋白水平以及提高 Bcl-2 蛋白水平来缓解 MEHP 诱导的细胞凋亡。这些结果表明，从牡蛎肽中提取的锌螯合肽可作为一种潜在的膳食锌补充剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Marine Drugs 医学-医药化学

CiteScore

9.60

自引率

14.80%

发文量

671

审稿时长

1 months

期刊介绍： Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.