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Redox Biol. 2018 May;15:207-215. doi: 10.1016/j.redox.2017.12.003. Epub 2017 Dec 15.

Oxalate induces mitochondrial dysfunction and disrupts redox homeostasis in a human monocyte derived cell line.

Author information

1
Department of Urology, University of Alabama at Birmingham, Birmingham, AL, United States.
2
Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL, United States.
3
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States.
4
Department of Urology, University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address: taneciam@uab.edu.

Abstract

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 24h. 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.

KEYWORDS:

Calcium oxalate; Kidney stones; Mitochondria; MnSOD; Monocytes; Sodium oxalate

PMID:
29272854
PMCID:
PMC5975227
DOI:
10.1016/j.redox.2017.12.003
[Indexed for MEDLINE]
Free PMC Article

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