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Peroxiredoxin 6 regulates the phosphoinositide 3-kinase/AKT pathway to maintain human sperm viability.
Molecular Human Reproduction ( IF 4 ) Pub Date : 2019-12-01 , DOI: 10.1093/molehr/gaz060
Maria C Fernandez 1, 2 , Alex Yu 1, 2 , Adel R Moawad 1, 2, 3 , Cristian O'Flaherty 1, 2, 4
Affiliation  

Peroxiredoxins (PRDXs) are antioxidant enzymes proven to control the levels of reactive oxygen species (ROS) and to avoid oxidative damage in the spermatozoon. Previously, we have shown that low amounts of PRDXs are associated with male infertility and that PRDX6 is the primary antioxidant defense in human spermatozoa, maintaining survival and DNA integrity (Gong et al., 2012, Fernandez and O'Flaherty, 2018). Oxidative stress can trigger different pathway cascades in the spermatozoa, including truncated apoptosis. It has been reported that the phosphorylation status of phosphoinositide 3-kinase (PI3K) and its target AKT (protein kinase B) prevent the spermatozoon from entering the truncated apoptotic cascade. Here, we aim to study the regulation of the PI3K/AKT pathway by PRDX6 and assess its role in maintaining sperm viability. Human semen samples were obtained over 1 year from 20 healthy non-smoking volunteers aged 22-30 years. Sperm viability, lipid peroxidation and apoptosis-like changes were determined by flow cytometry while phosphorylation of PI3K and AKT substrates were assessed by immunoblotting using anti-phospho-PI3K and anti-phospho-AKT substrates antibodies. We found that the addition of arachidonic acid and lysophosphatidic acid, products of PRDX6 calcium-independent phospholipase A2 (Ca2+-iPLA2), prevented loss of sperm viability and maintained the phosphorylation of PI3K. Antioxidant compounds such as D-penicillamine partially prevented the oxidative damage on spermatozoa that led to a reduction of their viability. Thus, other pathways can also participate in sperm survival and be regulated by PRDXs. In conclusion, PRDX6 contributes to the regulation of ROS production and the PI3K/AKT pathway for the maintenance of sperm survival.

中文翻译:

过氧化物酶6调节磷酸肌醇3-激酶/ AKT途径,以维持人类精子的生存能力。

Peroxiredoxins(PRDXs)是一种抗氧化酶,经证实可控制活性氧(ROS)的水平并避免精子中的氧化损伤。以前,我们已经证明低含量的PRDXs与男性不育有关,并且PRDX6是人类精子的主要抗氧化防御剂,可以维持生存和DNA完整性(Gong等,2012; Fernandez和O'Flaherty,2018)。氧化应激可以触发精子中不同的途径级联反应,包括截短的细胞凋亡。据报道,磷酸肌醇3-激酶(PI3K)及其靶标AKT(蛋白激酶B)的磷酸化状态阻止了精子进入截短的凋亡级联反应。在这里,我们旨在研究PRDX6对PI3K / AKT途径的调控,并评估其在维持精子生存能力中的作用。超过1年的时间从​​20岁至30岁的健康非吸烟志愿者那里获得了人类精液样本。通过流式细胞术确定精子的活力,脂质过氧化和凋亡样变化,同时使用抗磷酸-PI3K和抗磷酸-AKT底物抗体通过免疫印迹评估PI3K和AKT底物的磷酸化。我们发现,添加花生四烯酸和溶血磷脂酸(PRDX6钙非依赖性磷脂酶A2(Ca2 + -iPLA2)的产物)可防止精子活力丧失并维持PI3K的磷酸化。抗氧化剂化合物(例如D-青霉胺)部分阻止了精子的氧化损伤,从而导致其活力降低。因此,其他途径也可以参与精子存活并受到PRDX的调节。结论,
更新日期:2019-11-01
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