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ISSN Печать: 0731-8898
ISSN Онлайн: 2162-6537
Indexed in
Investigating the Role of Mitochondrial Respiratory Dysfunction during Hexavalent Chromium-Induced Lung Carcinogenesis
Краткое описание
Hexavalent chromium [Cr(VI)] is a lung carcinogen and its complete mechanism of action remains to be investigated. Metabolic reprogramming of key energy metabolism pathways (e.g., increased anaerobic glycolysis in the presence of oxygen or "Warburg effect", dysregulated mitochondrial function, and lipogenesis) are important to cancer cell and tumor survival and growth. In our current understanding of Cr(VI)-induced carcinogenesis, the role for metabolic reprogramming remains unclear. In this study, we treated human lung epithelial cells (BEAS-2B) with Cr(VI) for 6 months and obtained malignantly transformed cells from an isolated colony grown in soft agar. We also used Cr(VI)-transformed cells from two other human lung cell lines (BEP2D and WTHBF-6 cells). Overall, we found that all the Cr(VI)-transformed cells had no changes in their mitochondrial respiratory functions (measured by the Seahorse Analyzer) compared with passaged-matched control cells. Using a xenograft tumor growth model, we generated tumors from these transformed cells in Nude mice. Using cells obtained from the xenograft tumor tissues, we observed that these cells had decreased maximal mitochondrial respiration, spare respiratory capacity, and coupling efficiency. These results provide evidence that, although mitochondrial dysfunction does not occur during Cr(VI)-induced transformation of lung cells, it does occur during tumor development.
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Xue Song, Xu Yiming, Xu Shenglin, Zhong Yiming, Ruan Guangfeng, Ma Jinzhong, Hu Yong, Ding Changhai, Sang Weilin, Mitophagy impairment mediates the pathogenesis of CoCrMo particle-induced osteolysis via NLRP3/caspase-1/GSDMD-dependent pyroptosis in macrophages, Chemical Engineering Journal, 435, 2022. Crossref
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Bao Shibo, Zhang Cong, Luo Shengxiang, Jiang Liping, Li Qiujuan, Kong Ying, Cao Jun, HMGA2 mediates Cr (VI)-induced metabolic reprogramming through binding to mitochondrial D-Loop region, Ecotoxicology and Environmental Safety, 244, 2022. Crossref