Myoglobin mutant with enhanced nitrite reductase activity regulates intracellular oxidative stress in human breast cancer cells.
Myoglobin mutant with enhanced nitrite reductase activity regulates intracellular oxidative stress in human breast cancer cells.
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DOI：
10.1016/j.abb.2022.109399
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发表时间：
2022-09
影响因子：
3.9
通讯作者：
Xin-Yi Tong;Xin-Zhi Yang;Xinchen Teng;Shuqin Gao;G. Wen;Ying-Wu Lin
中科院分区：
文献类型：
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作者：
Xin-Yi Tong;Xin-Zhi Yang;Xinchen Teng;Shuqin Gao;G. Wen;Ying-Wu Lin
血红素蛋白在调节细胞内活性氧/氮（ROS/RNS）水平中起重要作用。在这项研究中，我们在典型的代表性三阴性乳腺癌细胞MDA-MB-231细胞中过表达人野生型（WT）肌红蛋白（Mb）及其具有增强的亚硝酸盐还原酶（NIR）活性的双突变体F43 H/H64 A Mb。结果表明，F43 H/H64 A Mb的过表达增加了一氧化氮（NO）水平和氧化应激程度，激活了Akt/MAPK介导的凋亡级联反应，而WT Mb则相反。这项研究表明，Mb在维持细胞氧化还原系统的平衡中起着重要作用，因此可能是一个有价值的癌症治疗靶点。
Heme proteins play vital roles in regulating the reactive oxygen/nitrogen species (ROS/RNS) levels in cells. In this study, we overexpressed human wild-type (WT) myoglobin (Mb) and its double mutant, F43H/H64A Mb with enhanced nitrite reductase (NIR) activity, in the typical representative triple-negative breast cancer cell, MDA-MB-231 cells. The results showed that the overexpression of F43H/H64A Mb increased the level of nitric oxide (NO) and the degree of oxidative stress, and then activated Akt/MAPK mediated apoptotic cascade, whereas WT Mb showed the opposite effect. This study indicates that Mb plays an important role in maintaining the balance of the cellular redox system and could thus be a valuable target for cancer therapy.