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

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.

Effect of moonseed vine (Triclisia gilletii Staner) on ethane-1,2-diol-induced urolithiasis and its renotoxicity in Wistar albino rats

“…Therefore, the observed damage to the kidney in the animals is as a result of oxalate or calcium oxalate [41]. In this present study, TGME showed a protective effect in the damage caused by metabolic alkalosis due to excess bicarbonate generated from low-dose ethane-1,2-diol.…”

“…Oleanolic acid is a known anti-inflammatory agent [50]. Mitochondrial function is important in regulating energy production and redox signaling which is usually impaired in patients with CaOx kidney stone disease [41,51]. Hence, markers suggesting membrane damage were investigated in this study via complex 1 activity, Na-K ATPase activity, glutamine synthetase activity, and lactate dehydrogenase activity.…”

“…Also, (Na + -K + ) adenosine triphosphatase (ATPase), which is localized to the basolateral membrane, is responsible for tubular re-absorptive process and regulated by direct interactions with membrane-associated cytoskeletal proteins that are also susceptible to oxidative damage [53]. The presence of calcium or calcium oxalate had been linked with the reorganization of the actin cytoskeleton, and it is believed to be important in the surface membrane structural, biochemical, and functional alterations in tubules [41].…”

Gut microbial diversity across a contact zone for California voles: Implications for lineage divergence of hosts and mitonuclear mismatch in the assembly of the mammalian gut microbiome

“…More specifically, the genus Anaerosporobacter has been shown to increase in abundance in association with acute respiratory distress syndrome (Li et al., 2014) and nonalcoholic fatty liver disease (Wong et al., 2013), both of which are linked to mitochondrial dysfunction (Wei, Rector, Thyfault, & Ibdah, 2008) or pathology (Li et al., 2014). Bacteria in the Family Oxalobacteraceae, which are also heritable in humans (Goodrich et al., 2016), are important in oxalate metabolism (Miller, Dale, & Dearing, 2017); in humans with kidney stone disease, oxalate induces a reduction in the mitochondrial functioning of immune cells (Patel et al., 2018), suggesting a potential link to host mitochondrial genotype. While these potential functional links to host genotype are intriguing, studies on how gut microbial functions are affected by the interactions between three genomes (mitochondrial, nuclear and gut microbiome) are still limited.…”

Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: A mechanism involving calcium overload/XO/ROS/mPTP pathway

“…The ROS was measured with 2′,7′-dichlorofluorescein-diacetate (DCFHDA, Beyotime Institute of Biotechnology, Jiangsu, China) and dihydroethidium (DHE, Invitrogen, San Diego, CA, USA) staining, and observed using a microscope or analysed by flow cytometry [27] . DCFHDA was alternately excited at the wavelengths of 488 nm and 525 nm and DHE was alternately excited at the wavelengths of 300 nm and 535 nm following the manufacturer's instructions.…”