期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 30, 期 2, 页码 198-212出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2017.7063
关键词
mitochondrial ferritin; HIF-1 alpha; hypoxia-induced apoptosis; ROS
资金
- National Natural Science Foundation of China [31520103908, 31471035, 31300898, 31271473]
- China Scholarship Council (CSC)
Aims: Mitochondrial ferritin (protein [FtMt]) is preferentially expressed in cell types of high metabolic activity and oxygen consumption, which is consistent with its role of sequestering iron and preventing oxygen-derived redox damage. As of yet, the mechanisms of FtMt regulation and the protection FtMt affords remain largely unknown. Results: Here, we report that hypoxia-inducible factor 1 alpha (HIF-1 alpha) can upregulate FtMt expression. We verify one functional hypoxia-response element (HRE) in the positive regulatory region and two HREs possessing HIF-1 alpha binding activity in the minimal promoter region of the human FTMT gene. We also demonstrate that FtMt can alleviate hypoxia-induced brain cell death by sequestering uncommitted iron, whose levels increase with hypoxia in these cells. Innovation: In the absence of FtMt, this catalytic metal excess catalyzes the production of cytotoxic reactive oxygen species. Conclusion: Thus, the cell ability to increase expression of FtMt during hypoxia may be a skill to avoid tissue damage derived from oxygen limitation.
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