Peng Chen,Na Geng,Dong Zhou,Yiran Zhu,Yuliang Xu,Kangping Liu,Yongxia Liu,Jianzhu Liu
Hexavalent chromium (Cr(VI)) is a common environmental pollutant. Exposure of Cr(VI) can lead to cell autophagy, but the preventive measures for diminishing Cr(VI)-induced autophagy need further study. COX-2 can be induced by several heavy metals and can lead to endoplasmic reticulum (ER) stress and autophagy; thus, COX-2, ER stress, and autophagy may be related. This study mainly investigated the role of COX-2 in the eIF2α-ATF4 pathway, which is a major pathway in cell autophagy. In this study, Cr(VI) was used as a xenobiotic to determine changes in the parameters of ER stress, autophagy, and COX-2 levels. At the same time, a clear contrast was obtained by assigning positive and negative controls of ER stress and autophagy. The results showed that during Cr(VI) invasion, the parameters of ER stress and autophagy (such as BiP, PERK, p62, LC3-II, and mTOR) were enhanced, similarly to the positive control of ER stress and/or the autophagy controls. Such enhancement is a protective mechanism for cell survival. Additionally, the COX-2 levels increased. Moreover, when COX-2 was inhibited, the PERK level remained high, whereas the LC3-II level decreased. This finding suggests that COX-2 specifically affects the interaction between ER stress and autophagy. Notably, this study reveals that Cr(VI) can induce ER stress and autophagy in DF-1 cells and that COX-2 plays an essential role in the interaction between ER stress and autophagy.
Yuliang Xu,Xiaozhou Wang,Na Geng,Yiran Zhu,Shuo Zhang,Yongxia Liu,Jianzhu Liu
Cr (VI), which is a common heavy metal pollutant with strong oxidizing property, exists widely in nature. Organisms can be exposed to Cr (VI) through various means. Cr (VI) causes mitochondrial dysfunction after being absorbed by cells. Whether Cr (VI) induces the selective autophagic degradation of mitochondria, which is a biological process called mitophagy, remains unclear. Mitophagy not only recycles intracellularly damaged mitochondria to compensate for nutrient deprivation but also is involved in mitochondria quality control. Thus, this study investigated whether Cr (VI) could induce mitophagy in DF-1 cells. Carbonyl cyanide m-chlorophenylhydrazone, which is a mitochondrial-uncoupling reagent that induces mitophagy, was used. DF-1 cells were incubated with different doses of Cr (VI) for varying durations. The autophagy-related proteins LC3-II and p62 levels decreased after 6 h of Cr (VI) treatment but recovered within 24 h. The mitochondrial membrane potential, which is an indicator of mitochondrial damage, was detected by flow cytometry. We found that different durations of Cr (VI) treatment induced mitochondrial mass decrease and depolarization. Furthermore, the expression of the protein translocase of outer mitochondrial membrane 20 (TOMM20), which is a mitochondrial outer membrane protein, was decreased significantly in the presence of Cr (VI). Our findings indicate that Cr (VI) may contribute to the mitochondrial morphology and function damage and may therefore lead to the autophagic clearance of mitochondria.
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