Abstract
Diabetic neuropathy (DNP) is the most common complication of diabetes mellitus affecting approximately 50% of diabetes patients. Studying the effect of potential drugs with antioxidant properties and minimal toxicities on neural cells may lead to the development of new and safe pharmacotherapy. Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, is a clinically used sedative also known to have neural protection effect. In the present study, we aimed to investigate the protective role of DEX in high glucose (HG)-induced neural injury and its potential miRNA-related mechanisms. Our results showed that DEX exerted neuroprotective effects during high glucose-induced damage to PC12 cells in a dose-dependent manner. DEX restored cell viability and repressed LDH, Caspase-3 activity, ROS production, and cell apoptosis in HG-treated PC12 cells. MiR-125b-5p was significantly up-regulated in PC12 cells upon HG treatment and it was demonstrated as an target for DEX. The neuroprotective effects of DEX on HG-induced cellular injury were reversed through miR-125b-5p overexpression, and vitamin D receptor (VDR) is a direct targeted of the miR-125b-5p. Together, our results indicate that DEX displays neuroprotective effects on PC-12 cells under high glucose through regulating miR-125b-5p/VDR axis. Our findings might raise the possibility of potential therapeutic application of DEX for managing diabetic neuropathy neural injuries.
Highlights
Glucose is essential for normal neural activity, excessive glucose induced oxidative stress and neuronal cell injury
Equivalent concentrations of mannitol were used as an osmotic control and the results showed that high glucose (HG) had little effect on cell viability
The results indicate that the lactate dehydrogenase (LDH) and caspase-3 activity were markedly increased in PC12 under high-glucose conditions but significantly decreased upon treatment with 10 or 100 μM DEX and under high-glucose conditions (Figure 1D,E)
Summary
Glucose is essential for normal neural activity, excessive glucose induced oxidative stress and neuronal cell injury. Diabetic neuropathy (DNP), a heterogeneous group of disorders in patients with diabetes mellitus, involves damage or impaired function of the autonomic and/or peripheral nervous system [1]. More than 50% of individuals with diabetes are affected by DNP, the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care [2]. Elevated serum glucose levels even elevated the risk of Type 2 diabetes (T2DM) and DNP in the mother, and obesity, cardiovascular disease (CVD), and T2DM in the child [3,4]. Despite advances in understanding the etiology, and the significant individual and social burden associated with DNP, its treatment remains unsatisfactory. Many therapies have been the subject of clinical trials for DNP. There are currently no FDA-approved therapies for DNP.
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