HINT2 may be One Clinical Significance Target for Patient with Diabetes Mellitus and Reduced ROS-Induced Oxidative Stress and Ferroptosis by MCU
Horm Metab Res DOI: 10.1055/a-2238-2689The World Health Organization (WHO) predicted that patients with diabetes around
the world will increase to 600 million by 2040, of which about 1/3 will
develop diabetic nephropathy (DN). Therefore, the present study aimed to uncover
therapeutic effect of HINT2 and determined its possible mechanisms. Patients
with diabetes mellitus and normal volunteers were enrolled at our hospital. Male
C57BL/6 mice were fed with a high fat diet and injected
intraperitoneally with STZ for once (100 mg/kg body weight).
Mouse podocytes (MPC5) cells were induced with 20 mmol/l
D-glucose. Inhibition of HINT2 mRNA expression levels in patients with DN was
observed, compared with normal group. The serum of HINT2 mRNA expression was
negative in correlation with blood sugar, tubulo-interstitial damage, glomerular
damage score or urine protein level in patients with DN. HINT2 expression in
kidney tissue of mice with DN were downregulated. HINT2 presented reduced DN and
inflammation and ROS-induced oxidative stress in model of DN. HINT2 promoted
ferroptosis in model of DN by mitochondrial membrane potential. HINT2 suppressed
MCU expression in model of DN. HINT2 protein combined with MCU protein increased
MCU protein ubiquitination. HINT2 triggers mitochondrial Ca2+ influx to
increase ROS pro...
Source: Hormone and Metabolic Research - Category: Endocrinology Authors: Bai, Mei Lu, Wei Tan, Jun Mei, Xin Tags: Original Article: Endocrine Research Source Type: research
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