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  • Modulation of Renal Injury by Variable Expression of Myo-Inositol Oxygenase (MIOX) via Perturbation in Metabolic Sensors.

Modulation of Renal Injury by Variable Expression of Myo-Inositol Oxygenase (MIOX) via Perturbation in Metabolic Sensors.

Biomedicines (2020-07-28)
Isha Sharma, Fei Deng, Yashpal S Kanwar
ABSTRACT

Obesity is associated with perturbations in cellular energy homeostasis and consequential renal injury leading to chronic renal disease (CKD). Myo-inositol oxygenase (MIOX), a tubular enzyme, alters redox balance and subsequent tubular injury in the settings of obesity. Mechanism(s) for such adverse changes remain enigmatic. Conceivably, MIOX accentuates renal injury via reducing expression/activity of metabolic sensors, which perturb mitochondrial dynamics and, if sustained, would ultimately contribute towards CKD. In this brief communication, we utilized MIOX-TG (Transgenic) and MIOX KO mice, and subjected them to high fat diet (HFD) administration. In addition, ob/ob and ob/MIOX KO mice of comparable age were used. Mice fed with HFD had increased MIOX expression and remarkable derangements in tubular injury biomarkers. Decreased expression of p-AMPKα (phospho AMP-activated protein kinase) in the tubules was also observed, and it was accentuated in MIOX-TG mice. Interestingly, ob/ob mice also had decreased p-AMPKα expression, which was restored in ob/MIOX KO mice. Parallel changes were observed in Sirt1/Sirt3 (silent mating type information regulation 2 homolog), and expression of other metabolic sensors, i.e., PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and Yin Yang (YY-1). In vitro experiments with tubular cells subjected to palmitate-BSA and MIOX-siRNA had results in conformity with the in vivo observations. These findings link the biology of metabolic sensors to MIOX expression in impaired cellular energy homeostasis with exacerbation/amelioration of renal injury.

MATERIALS
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Product Description

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