Elsevier

Redox Biology

Volume 15, May 2018, Pages 207-215
Redox Biology

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

https://doi.org/10.1016/j.redox.2017.12.003Get rights and content
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Highlights

  • Oxalate is a major constituent of calcium oxalate (CaOx) kidney stones and can be found in either soluble or insoluble forms.

  • CaOx crystals are required for CaOx kidney stone formation.

  • Monocytes/macrophages play an important role in crystal clearance.

  • Oxalate causes mitochondrial dysfunction and disrupts redox homeostasis in monocytes.

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 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.

Abbreviations

ATP
adenosine triphosphate
CaOx
calcium oxalate
CaP
calcium phosphate
ECAR
extracellular acidification rate
GSH
glutathione
GSSG
glutathione disulfide
MnSOD
manganese superoxide dismutase
NaOx
sodium oxalate
OCR
oxygen consumption rate

Keywords

Mitochondria
Monocytes
Calcium oxalate
Sodium oxalate
Kidney stones
MnSOD

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