期刊
REDOX BIOLOGY
卷 15, 期 -, 页码 207-215出版社
ELSEVIER
DOI: 10.1016/j.redox.2017.12.003
关键词
Mitochondria; Monocytes; Calcium oxalate; Sodium oxalate; Kidney stones; MnSOD
资金
- UAB Faculty Development Grant Program, Office of the Provost
- NIH [P30 DK079337, P30 DK079626, 5K12GM088010, R01 DK054468, K01DK106284]
Monocytes/macrophages are thought to be recruited to the renal interstitium during calcium oxalate (CaOx) kidney stone disease for crystal clearance. Mitochondria play an important role in monocyte function during the immune response. We recently determined that monocytes in patients with CaOx kidney stones have decreased mitochondrial function compared to healthy subjects. The objective of this study was to determine whether oxalate, a major constituent found in CaOx kidney stones, alters cell viability, mitochondrial function, and redox homeostasis in THP-1 cells, a human derived monocyte cell line. THP-1 cells were treated with varying concentrations of CaOx crystals (insoluble form) or sodium oxalate (NaOx; soluble form) for 24 h. In addition, the effect of calcium phosphate (CaP) and cystine crystals was tested. CaOx crystals decreased cell viability and induced mitochondrial dysfunction and redox imbalance in THP-1 cells compared to control cells. However, NaOx only caused mitochondrial damage and redox imbalance in THP-1 cells. In contrast, both CaP and cystine crystals did not affect THP-1 cells. Separate experiments showed that elevated oxalate also induced mitochondrial dysfunction in primary monocytes from healthy subjects. These findings suggest that oxalate may play an important role in monocyte mitochondrial dysfunction in CaOx kidney stone disease.
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