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神经酰胺通过调节秀丽隐杆线虫中线粒体功能和 MAPK 因子介导辐射诱导的生殖细胞凋亡。

Ceramide mediates radiation-induced germ cell apoptosis via regulating mitochondria function and MAPK factors in Caenorhabditis elegans.

机构信息

Anhui Provincial Engineering Laboratory of Water and Soil Pollution Control and Remediation, School of Ecology and Environment, Anhui Normal University, Wuhu, Anhui 241002, China; Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China.

出版信息

Ecotoxicol Environ Saf. 2021 Jan 15;208:111579. doi: 10.1016/j.ecoenv.2020.111579. Epub 2020 Nov 6.

Abstract

Studies about radiation damage in vivo are very significant for healthy risk assessment as well as cancer radiotherapy. Ceramide as a second messenger has been found to be related to radiation-induced apoptosis. However, the detailed mechanisms in living systems are still not fully understood. In the present study, the effects of ceramide in gamma radiation-induced response were investigated using Caenorhabditis elegans. Our results indicated that ceramide was required for gamma radiation-induced whole-body germ cell apoptosis by the production of radical oxygen species and decrease of mitochondrial transmembrane potential. Using genetic ceramide synthase-related mutated strains and exogenous C-ceramide, we illustrated that ceramide could regulate DNA damage response (DDR) pathway to mediate radiation-induced germ cell apoptosis. Moreover, ceramide was found to function epistatic to pmk-1 and mpk-1 in MAPK pathway to promote radiation-induced apoptosis in Caenorhabditis elegans. These results demonstrated ceramide could potentially mediated gamma radiation-induced apoptosis through regulating mitochondrial function, DDR pathway and MAPK pathway.

摘要

研究体内辐射损伤对于健康风险评估以及癌症放射治疗非常重要。神经酰胺作为第二信使,已被发现与辐射诱导的细胞凋亡有关。然而,其在活细胞中的详细机制仍未完全阐明。本研究利用秀丽隐杆线虫(Caenorhabditis elegans)研究了神经酰胺在γ辐射诱导反应中的作用。结果表明,神经酰胺通过产生活性氧和降低线粒体跨膜电位,从而在γ辐射诱导的全身体细胞凋亡中发挥作用。利用遗传上相关的神经酰胺合酶突变株和外源性 C 神经酰胺,我们表明神经酰胺可以调节 DNA 损伤反应(DDR)途径来介导辐射诱导的生殖细胞凋亡。此外,还发现神经酰胺在丝裂原活化蛋白激酶(MAPK)途径中与 pmk-1 和 mpk-1 具有上位性,从而促进秀丽隐杆线虫中辐射诱导的细胞凋亡。这些结果表明,神经酰胺可能通过调节线粒体功能、DDR 途径和 MAPK 途径来介导 γ 辐射诱导的细胞凋亡。

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