Oxalate induces mitochondrial dysfunction and disrupts redox homeostasis in a human monocyte derived cell line
| Autor: | Dean G. Assimos, Vidhush K. Yarlagadda, Tanecia Mitchell, Vikram Saini, Oreoluwa O. Adedoyin, Ross P. Holmes, Mikita Patel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Calcium Phosphates
Male 0301 basic medicine MnSOD GSSG glutathione disulfide Clinical Biochemistry 030232 urology & nephrology Calcium oxalate Mitochondrion Kidney Biochemistry Monocytes chemistry.chemical_compound 0302 clinical medicine GSH glutathione Homeostasis OCR oxygen consumption rate lcsh:QH301-705.5 Oxalates lcsh:R5-920 Chemistry CaP calcium phosphate 3. Good health Mitochondria medicine.anatomical_structure lcsh:Medicine (General) Oxidation-Reduction Research Paper Adult medicine.medical_specialty ATP adenosine triphosphate Cell Survival Kidney stones chemistry.chemical_element Calcium Nephrolithiasis NaOx sodium oxalate Oxalate Cell Line 03 medical and health sciences Internal medicine medicine Humans Viability assay MnSOD manganese superoxide dismutase ECAR extracellular acidification rate Monocyte Organic Chemistry CaOx calcium oxalate 030104 developmental biology Endocrinology lcsh:Biology (General) Sodium oxalate |
| Zdroj: | Redox Biology, Vol 15, Iss C, Pp 207-215 (2018) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | 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. Graphical abstract fx1 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. |
| Databáze: | OpenAIRE |
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