Oxalate induces mitochondrial dysfunction and disrupts redox homeostasis in a human monocyte derived cell line.
Oxalate induces mitochondrial dysfunction and disrupts redox homeostasis in a human monocyte derived cell line.
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DOI：
10.1016/j.redox.2017.12.003
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发表时间：
2018-05
期刊：
影响因子：
11.4
通讯作者：
Mitchell T
中科院分区：
文献类型：
--
作者：
Patel M;Yarlagadda V;Adedoyin O;Saini V;Assimos DG;Holmes RP;Mitchell T
单核细胞/巨噬细胞被认为在草酸钙（CaOx）肾结石疾病期间被募集到肾间质以清除晶体。线粒体在免疫反应期间的单核细胞功能中起重要作用。我们最近确定，与健康受试者相比，草酸钙肾结石患者的单核细胞线粒体功能下降。本研究的目的是确定草酸（草酸钙肾结石中的一种主要成分）是否会改变THP - 1细胞（一种人源性单核细胞系）的细胞活力、线粒体功能和氧化还原稳态。THP - 1细胞用不同浓度的草酸钙晶体（不溶形式）或草酸钠（NaOx；可溶形式）处理24小时。此外，还测试了磷酸钙（CaP）和胱氨酸晶体的作用。与对照细胞相比，草酸钙晶体降低了THP - 1细胞的活力，并诱导了线粒体功能障碍和氧化还原失衡。然而，草酸钠仅导致THP - 1细胞的线粒体损伤和氧化还原失衡。相比之下，磷酸钙和胱氨酸晶体均不影响THP - 1细胞。单独的实验表明，升高的草酸也会诱导健康受试者原代单核细胞的线粒体功能障碍。这些发现表明，草酸可能在草酸钙肾结石疾病中的单核细胞线粒体功能障碍中起重要作用。
草酸是草酸钙（CaOx）肾结石的一种主要成分，可以以可溶或不可溶的形式存在。
草酸钙晶体是草酸钙肾结石形成所必需的。
单核细胞/巨噬细胞在晶体清除中起重要作用。
草酸导致单核细胞线粒体功能障碍并破坏氧化还原稳态。
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. 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.
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