SIRT5介导的PRKAA2琥珀酰化可改善妊娠高血压并发症中人胎盘滋养细胞的凋亡。

IF 1.5 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Clinical and Experimental Hypertension Pub Date : 2024-12-31 Epub Date: 2024-05-24 DOI:10.1080/10641963.2024.2358030
Feifei Ren, Mo Yang, Guangman Liu, Yuyan Qi, Aijie Li, Jia Li, Lili Zheng
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引用次数: 0

摘要

目的:妊娠合并高血压疾病(HDCP)是妊娠期一种严重的临床疾病综合征。方法:首先筛选出与 HDCP 相关的 mRNA,并对其进行基因富集分析。我们选择蛋白激酶 AMP 激活催化亚基α2(PRKAA2)作为研究对象。本研究选取了 39 名妊娠 32 至 40 周的 HDCP 患者作为 HDCP 组,39 名妊娠 37 至 42 周剖宫产的正常对照组作为 HDCP 组。在分娩后 30 分钟内采集绒毛样本。通过监测分离的胎盘滋养细胞的凋亡,研究PRKAA2的调控作用:结果:进一步证实,与正常孕妇相比,HDCP 患者胎盘组织中 PRKAA2 表达增强。随后,流式细胞术分析和免疫印迹的结果表明,PRKAA2 的过表达加速了原发性胎盘细胞的凋亡,而其敲除则减轻了细胞的凋亡。从机理上讲,我们发现 HDCP 患者胎盘组织中 PRKAA2 的琥珀酰化水平升高。通过体外琥珀酰化试验和诱变,我们证实了sirtuin 5(SIRT5)与PRKAA2在K69和K260处相互作用,诱导PRKAA2脱琥珀酰化。SIRT5通过PRKAA2调控原代HDCP细胞凋亡。最后,动物实验表明,PRKAA2 能升高 HDCP 大鼠模型的收缩压:我们的研究结果表明,SIRT5介导的PRKAA2琥珀酰化可调节HDCP中胎盘细胞的凋亡,这表明PRKAA2是治疗HDCP的潜在靶点。
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SIRT5-mediated PRKAA2 succinylation ameliorates apoptosis of human placental trophoblasts in hypertensive disorder complicating pregnancy.

Purpose: Hypertensive disorder complicating pregnancy (HDCP) is a serious clinical disorder syndrome during pregnancy. This study aims at finding novel targets for HDCP therapy.

Methods: HDCP-related mRNAs were firstly screened out and subjected to gene enrichment analysis. We chose protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) as the research object. Thirty-nine HDCP patients at 32 to 40 weeks of gestation were selected as the HDCP group, and 39 normal controls who received cesarean section delivery at 37-42 weeks of pregnancy were enrolled in this study. Chorionic villi samples were collected within 30 min of delivery. The apoptosis of isolated placental trophoblasts was monitored to investigate the regulatory role of PRKAA2.

Results: PRKAA2 expression was further proven to be enhanced in the placental tissues of HDCP patients compared with that of normal puerpera. Subsequently, the results of flow cytometry analysis and western blot indicated that PRKAA2 overexpression accelerated primary placental cell apoptosis, while its knockdown attenuated cell apoptosis. Mechanistically, we determined that the level of PRKAA2 succinylation was elevated in the placental tissue of HDCP patients. Through in vitro succinylation assay and mutagenesis, we confirmed that sirtuin 5 (SIRT5) interacts with PRKAA2 at K69 and K260 to induce PRKAA2 desuccinylation. SIRT5 regulated primary HDCP cell apoptosis through PRKAA2. Finally, the animal study revealed that PRKAA2 elevates the systolic blood pressure of HDCP rat model.

Conclusion: Our findings indicated that SIRT5-mediated PRKAA2 succinylation modulates placental cell apoptosis in HDCP, suggesting that PRKAA2 is a potential therapeutic target for HDCP treatment.

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来源期刊
CiteScore
3.90
自引率
0.80%
发文量
66
审稿时长
6-12 weeks
期刊介绍: Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.
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