硒代胱氨酸通过 ROS 介导的 PARP 和 p53 信号通路抑制 HAdV-14 诱导的细胞凋亡,Journal of Trace Elements in Medicine and Biology

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硒代胱氨酸通过 ROS 介导的 PARP 和 p53 信号通路抑制 HAdV-14 诱导的细胞凋亡
Journal of Trace Elements in Medicine and Biology ( IF 3.6 ) Pub Date : 2023-05-18 , DOI: 10.1016/j.jtemb.2023.127213
Ruilin Zheng ₁ , Danyang Chen ₁ , Jingyao Su ₁ , Jia Lai ₁ , Chenyang Wang ₁ , Haitian Chen ₁ , Zhihui Ning ₁ , Xia Liu ₁ , Xingui Tian ₂ , Yinghua Li ₁ , Bing Zhu ₁

Affiliation

背景

人类腺病毒（HAdV）可导致免疫力低下的人出现严重的呼吸道症状，并且腺病毒感染没有针对性的治疗方法。抗腺病毒药物对于抑制腺病毒感染具有较高的临床意义。硒（Se）在抗氧化、氧化还原信号转导和氧化还原稳态中发挥着重要作用。Se的优异生物活性主要是通过转化为硒代胱氨酸（SeC）来实现的。Se 以 SeC 的形式参与各种硒蛋白的活性位点。近年来，SeC因其独特的抗氧化活性，抵抗病毒的能力引起了人们的高度关注。通过检测细胞内病毒的感染率来判断SeC的抗病毒能力。

方法

实验主要通过细胞内病毒定位、检测ROS的产生、观察细胞DNA状态、监测线粒体膜电位等研究SeC的抗病毒机制。

结果

在本研究中，SeC 旨在抵抗 HAdV-14 引起的 A549 细胞感染。SeC 可以阻止 HAdV-14 引起与 DNA 损伤相关的细胞凋亡。SeC 显着抑制 ROS 生成，并保护细胞免受 ROS 诱导的 HAdV-14 氧化损伤。SeC通过激活Jak2信号通路诱导IL-6和IL-8等抗病毒细胞因子的增加，并通过抑制ATR、p53和PARP信号通路修复DNA损伤。

结论

SeC 可能为 HAdV-14 的治疗提供具有抗病毒特性的有效硒物质。

"点击查看英文标题和摘要"

Inhibition of HAdV-14 induced apoptosis by selenocystine through ROS-mediated PARP and p53 signaling pathways

Background

Human Adenovirus (HAdV) can cause severe respiratory symptoms in people with low immunity and there is no targeted treatment for adenovirus infection. Anti-adenoviral drugs have high clinical significance for inhibiting adenovirus infection. Selenium (Se) plays an important role in anti-oxidation, redox signal transduction, and redox homeostasis. The excellent biological activity of Se is mainly achieved by being converted into selenocystine (SeC). Se participates in the active sites of various selenoproteins in the form of SeC. The ability of SeC to resist the virus has raised high awareness due to its unique antioxidative activity in recent years. The antiviral ability of the SeC was determined by detecting the infection rate of the virus in the cells.

Methods

The experiment mainly investigated the antiviral mechanism of SeC by locating the virus in the cell, detecting the generation of ROS, observing the DNA status of the cell, and monitoring the mitochondrial membrane potential.

Results

In the present study, SeC was designed to resist A549 cells infections caused by HAdV-14. SeC could prevent HAdV-14 from causing cell apoptosis-related to DNA damage. SeC significantly inhibited ROS generation and protect the cells from oxidative damage induced by ROS against HAdV-14. SeC induced the increase of antiviral cytokines such as IL-6 and IL-8 by activating the Jak2 signaling pathway, and repaired DNA lesions by suppressing ATR, p53, and PARP signaling pathways.