Background and Objective:
Glucose fluctuation (GF) has been reported to induce renal injury and
diabetic nephropathy (DN). However, the mechanism still remains ambiguous. Mitochondrial energy metabolism, especially aerobic glycolysis, has been a hotspot of DN research for decades. The activation of HIF-1α/miR210/
ISCU/FeS axis has provided a new explanation for aerobic glycolysis. Our previous studies indicated
quercetin as a potential therapeutic
drug for DN. This study aims to evaluate levels of aerobic glycolysis and repressive effect of
quercetin via HIF-1α/miR210/
ISCU/FeS axis in a cell model of GF. Methods: The mouse glomerular mesangial cells (MCs) were exposed in high or oscillating
glucose with or without
quercetin treatment. Cell viability was measured by CCK8 assay. Aerobic glycolysis flux was evaluated by
lactate acid, pH activity of PFK. Apoptosis level was confirmed by
Annexin V-APC/7-AAD double staining and activity of
caspase-3. TNF-α and IL-1β were used to evaluate
inflammation levels. Results: GF deteriorated
inflammation damage and apoptosis injury in MCs, while
quercetin could alleviate this GF-triggered cytotoxicity. GF intensified aerobic glycolysis in MCs and
quercetin could inhibit this intensification in a dose-dependent manner.
Quercetin prevented activities of two FeS-dependent metabolic
enzymes,
aconitase, and complex I, under GF injury in MCs. The
mRNA expression and
protein contents of HIF-1α were increased after GF exposure, and these could be alleviated by
quercetin treatment. Knockdown of
ISCU by
siRNA and Up-regulating of miR-210 by mimic could weaken the effects of
quercetin that maintained
protein levels of ISCU1/2, improved cell viability, relieved
inflammation injury, decreased apoptosis, and reduced aerobic glycolysis switch in MCs. Conclusion:
Quercetin antagonizes GF-induced renal injury by suppressing aerobic glycolysis via HIF-1α/miR-210/
ISCU/FeS pathway in MCs cell model. Our findings contribute to a new insight into understanding the mechanism of GF-induced renal injury and protective effects of
quercetin.