l-Carnitine protects against 1,4-benzoquinone-induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells
l-Carnitine protects against 1,4-benzoquinone-induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells
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左旋肉碱通过抑制 K562 细胞中的氧化应激和促进脂肪酸氧化来防止 1,4-苯醌诱导的细胞凋亡和 DNA 损伤
DOI：
10.1002/tox.22939
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发表时间：
2020
影响因子：
4.5
通讯作者：
Pu Yuepu
中科院分区：
文献类型：
--
作者：
Sun Rongli;Man Zhaodi;Ji Jiahui;Ji Shuangbin;Xu Kai;Pu Yunqiu;Yu Linling;Zhang Juan;Yin Lihong;Pu Yuepu
广泛的职业和环境接触苯是不可避免的，并构成公共健康威胁。因此，研究预防或减轻苯毒性的潜在干预措施至关重要。研究表明，左旋肉碱（LC）对各种病理过程和疾病具有有益作用。LC具有抗氧化活性，参与脂肪酸氧化（FAO）。在这项研究中，我们研究了1，4-苯醌（1，4-BQ）是否影响LC水平和FAO途径，并分析了LC对1，4-BQ细胞毒性作用的影响。我们发现1，4-BQ显著降低了K562细胞的LC水平，下调了Cpt 1a、Cpt 2、Crat、Hadha、Acadv 2和Acadv 1 mRNA的表达。随后的试验证实，1，4-BQ降低了细胞活力，增加了细胞凋亡和caspase-3、-8和-9活性。同时，还引起了明显的氧化应激和DNA损伤，包括活性氧和丙二醛水平、尾DNA%和Olive尾矩的增加。此外，线粒体膜电位显著降低。与LC（500 μmol/L）共处理通过降低氧化应激和增加Cpt 1a和Hadha的蛋白表达水平来缓解这些变化，特别是在20 μmol/L 1，4-BQ组。因此，我们的研究结果表明，1，4-BQ引起细胞毒性，降低LC水平，并下调FAO基因。相反，LC通过降低氧化应激和促进FAO途径对1，4-BQ诱导的细胞凋亡和DNA损伤具有保护作用。
Widespread occupational and environmental exposure to benzene is unavoidable and poses a public health threat. Studies of potential interventions to prevent or relieve benzene toxicity are, thus, essential. Research has shownl‐carnitine (LC) has beneficial effects against various pathological processes and diseases. LC possesses antioxidant activities and participates in fatty acid oxidation (FAO). In this study, we investigated whether 1,4‐benzoquinone (1,4‐BQ) affects LC levels and the FAO pathway, as well as analyzed the influence of LC on the cytotoxic effects of 1,4‐BQ. We found that 1,4‐BQ significantly decreased LC levels and downregulated Cpt1a, Cpt2, Crat, Hadha, Acaa2, and Acadvl mRNA expression in K562 cells. Subsequent assays confirmed that 1,4‐BQ decreased cell viability and increased apoptosis and caspase‐3, ‐8, and ‐9 activities. It also induced obvious oxidative stress and DNA damage, including an increase in the levels of reactive oxygen species and malondialdehyde, tail DNA%, and olive tail moment. Additionally, the mitochondrial membrane potential was significantly reduced. Cotreatment with LC (500 μmol/L) relieved these alterations by reducing oxidative stress and increasing the protein expression levels of Cpt1a and Hadha, particularly in the 20 μmol/L 1,4‐BQ group. Thus, our results demonstrate that 1,4‐BQ causes cytotoxicity, reduces LC levels, and downregulates the FAO genes. In contrast, LC exhibits protective effects against 1,4‐BQ‐induced apoptosis and DNA damage by decreasing oxidative stress and promoting the FAO pathway.