N-硫代羧酸酐，一种由氨基酸衍生而来的酶激活的 HS 供体，在存在和不存在氧化应激的情况下增强精子线粒体的活性。
N-thiocarboxyanhydrides, amino acid-derived enzyme-activated HS donors, enhance sperm mitochondrial activity in presence and absence of oxidative stress.
机构信息
Department of Veterinary Sciences, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, 16500, Prague, Czech Republic.
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA.
出版信息
BMC Vet Res. 2023 Feb 16;19(1):52. doi: 10.1186/s12917-023-03593-5.
BACKGROUND
Hydrogen sulfide (HS) donors are crucial tools not only for understanding the role of HS in cellular function but also as promising therapeutic agents for oxidative stress-related diseases. This study aimed to explore the effect of amino acid-derived N-thiocarboxyanhydrides (NTAs), which release physiological HS levels in the presence of carbonic anhydrase, on porcine sperm function during short-term incubation with and without induced oxidative stress. For this purpose, we employed two HS-releasing NTAs with release half-lives (t) in the range of hours that derived from the amino acids glycine (Gly-NTA) or leucine (Leu-NTA). Because carbonic anhydrase is crucial for HS release from NTAs, we first measured the activity of this enzyme in the porcine ejaculate. Then, we tested the effect of Gly- and Leu-NTAs at 10 and 1 nM on sperm mitochondrial activity, plasma membrane integrity, acrosomal status, motility, motile subpopulations, and redox balance during short-term incubation at 38 °C with and without a reactive oxygen species (ROS)-generating system.
RESULTS
Our results show that carbonic anhydrase is found both in spermatozoa and seminal plasma, with activity notably higher in the latter. Both Gly- and Leu-NTAs did not exert any noxious effects, but they enhanced sperm mitochondrial activity in the presence and absence of oxidative stress. Moreover, NTAs (except for Leu-NTA 10 nM) tended to preserve the sperm redox balance against the injuries provoked by oxidative stress, which provide further support to the antioxidant effect of HS on sperm function. Both compounds also increased progressive motility over short-term incubation, which may translate into prolonged sperm survival.
CONCLUSIONS
The presence of carbonic anhydrase activity in mammalian spermatozoa makes NTAs promising molecules to investigate the role of HS in sperm biology. For the first time, beneficial effects of NTAs on mitochondrial activity have been found in mammalian cells in the presence and absence of oxidative stress. NTAs are interesting compounds to investigate the role of HS in sperm mitochondria-dependent events and to develop HS-related therapeutic protocols against oxidative stress in assisted reproductive technologies.
背景
硫化氢 (HS) 供体不仅是研究 HS 在细胞功能中作用的重要工具，也是治疗与氧化应激相关疾病的有前途的治疗剂。本研究旨在探讨氨基酸衍生的 N-硫代羧基酰亚胺 (NTAs) 在存在碳酸酐酶的情况下释放生理 HS 水平对短期孵育过程中猪精子功能的影响，包括诱导氧化应激前后。为此，我们使用了两种半衰期 (t) 在小时范围内的 HS 释放 NTAs，它们分别来自氨基酸甘氨酸 (Gly-NTA) 或亮氨酸 (Leu-NTA)。由于碳酸酐酶对 NTAs 释放 HS 至关重要，我们首先测量了猪精液中这种酶的活性。然后，我们测试了 Gly-NTA 和 Leu-NTA 在 10 和 1 nM 浓度下对精子线粒体活性、质膜完整性、顶体状态、运动能力、运动亚群和氧化还原平衡的影响，这些影响是在 38°C 下短期孵育时产生的，有或没有活性氧 (ROS) 生成系统。
结果
我们的结果表明，碳酸酐酶存在于精子和精浆中，后者中的活性明显更高。Gly-NTA 和 Leu-NTA 都没有产生任何有害影响，但它们增强了有或没有氧化应激存在时的精子线粒体活性。此外，NTAs（除了 Leu-NTA 10 nM）倾向于在氧化应激引起的损伤下保持精子的氧化还原平衡，这进一步支持了 HS 对精子功能的抗氧化作用。两种化合物还增加了短期孵育过程中的渐进运动能力，这可能转化为精子存活时间的延长。
结论
碳酸酐酶活性存在于哺乳动物精子中，这使得 NTAs 成为研究 HS 在精子生物学中作用的有前途的分子。首次发现 NTAs 在存在和不存在氧化应激的情况下对哺乳动物细胞中线粒体活性具有有益作用。NTAs 是研究 HS 与精子线粒体依赖性事件的有趣化合物，也是开发 HS 相关治疗方案以对抗辅助生殖技术中氧化应激的有前途的化合物。
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