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化合物 YK 3-237 促进猪精子获能相关事件。

The compound YK 3-237 promotes pig sperm capacitation-related events.

机构信息

Departamento de Fisiología, Facultad de Medicina y Ciencias de la Salud, Universidad de Extremadura, Avenida de Elvas s/n, Badajoz, 06006, España.

Grupo de Investigación Señalización Intracelular y Tecnología de la Reproducción (SINTREP), Instituto de Investigación INBIO G+C. Universidad de Extremadura, Cáceres, España.

出版信息

Vet Res Commun. 2024 Apr;48(2):773-786. doi: 10.1007/s11259-023-10243-6. Epub 2023 Oct 31.

DOI:10.1007/s11259-023-10243-6
PMID:37906355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10998788/
Abstract

Before fertilization of the oocyte, the spermatozoa must undergo through a series of biochemical changes in the female reproductive tract named sperm capacitation. Spermatozoa regulates its functions by post-translational modifications, being historically the most studied protein phosphorylation. In addition to phosphorylation, recently, protein acetylation has been described as an important molecular mechanism with regulatory roles in several reproductive processes. However, its role on the mammal's sperm capacitation process remains unraveled. Sirtuins are a deacetylase protein family with 7 members that regulate protein acetylation. Here, we investigated the possible role of SIRT1 on pig sperm capacitation-related events by using YK 3-237, a commercial SIRT1 activator drug. SIRT1 is localized in the midpiece of pig spermatozoa. Protein tyrosine phosphorylation (focused at p32) is an event associated to pig sperm capacitation that increases when spermatozoa are in vitro capacitated in presence of YK 3-237. Eventually, YK 3-237 induces acrosome reaction in capacitated spermatozoa: YK 3-237 treatment tripled (3.40 ± 0.40 fold increase) the percentage of acrosome-reacted spermatozoa compared to the control. In addition, YK 3-237 induces sperm intracellular pH alkalinization and raises the intracellular calcium levels through a CatSper independent mechanism. YK 3-237 was not able to bypass sAC inhibition by LRE1. In summary, YK 3-237 promotes pig sperm capacitation by a mechanism upstream of sAC activation and independent of CatSper calcium channel.

摘要

在卵母细胞受精之前，精子必须在女性生殖道中经历一系列称为精子获能的生化变化。精子通过翻译后修饰来调节其功能，其中历史上研究最多的是蛋白磷酸化。除了磷酸化之外，最近，蛋白乙酰化已被描述为一种重要的分子机制，在几种生殖过程中具有调节作用。然而，它在哺乳动物精子获能过程中的作用仍未被揭示。Sirtuins 是一个去乙酰化酶蛋白家族，有 7 个成员，调节蛋白乙酰化。在这里，我们通过使用 YK 3-237（一种商业 SIRT1 激活药物）研究了 SIRT1 在猪精子获能相关事件中的可能作用。SIRT1 定位于猪精子的中段。蛋白酪氨酸磷酸化（集中在 p32）是与猪精子获能相关的一个事件，当精子在含有 YK 3-237 的体外条件下获能时，其磷酸化程度增加。最终，YK 3-237 诱导获能精子发生顶体反应：与对照组相比，YK 3-237 处理使顶体反应的精子比例增加了两倍（3.40±0.40 倍增加）。此外，YK 3-237 通过一种不依赖于 CatSper 的机制诱导精子细胞内 pH 值碱化并提高细胞内钙离子水平。YK 3-237 不能绕过 sAC 抑制物 LRE1。总之，YK 3-237 通过一种独立于 CatSper 钙通道且在 sAC 激活上游的机制促进猪精子获能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616a/10998788/0b033d836e24/11259_2023_10243_Fig7_HTML.jpg
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本文引用的文献

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The CASR antagonist NPS2143 induces loss of acrosomal integrity and proteolysis of SPACA1 in boar spermatozoa.钙敏感受体拮抗剂NPS2143可导致公猪精子顶体完整性丧失及精子相关抗原1（SPACA1）的蛋白水解。
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The sirtuin 1 activator YK 3-237 stimulates capacitation-related events in human spermatozoa.沉默调节蛋白1激活剂YK 3-237刺激人类精子发生获能相关事件。
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Protein acetylation protects sperm from spontaneous acrosome reaction.
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