Dexmedetomidine exerts neuroprotective effects during high glucose-induced neural injury by inhibiting miR-125b

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.

Protective effect of dexmedetomidine on neuronal hypoxic injury through inhibition of miR-134

“…36,37 In this study, qRT-PCR revealed that DEX alleviates H 2 O 2 -induced PC12 cell apoptosis, downregulates the expression of cleaved caspase-3, and upregulates the expression of Bcl-2. 31,34,38 Furthermore, this phenomenon could be reversed by the overexpression of miR-134, and HIBD pathology in neonatal rats and OGD-induced neuronal death in PC12 cells could be prevented by miR-134 inhibition. 28 Thus, these results indicate that H 2 O 2 -induced PC12 cell apoptosis can be inhibited by DEX by reducing miR-134 levels.…”

“…17 Furthermore, DEX exerted neuroprotective effects on PC12 cells under high glucose by regulating the miR-125b-5p/VDR axis. 31 Accumulating evidence suggests that oxidative stress induces inflammation and tissue damage. Notably, after LPS treatment, the levels of miR-134, IL-1b, and TNF-a were significantly increased in the hippocampus and cortex but decreased after DEX treatment, indicating…”

The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies

“…In PC12 cells with high glucose to induce DN, dexmedetomidine reduced ROS formation and neuronal 2A -adrenoceptor (Ma et al, 2004) apoptosis by inhibiting miR-125b-5p expression, which regulates gene expression related to apoptosis, autophagy, cell proliferation, metabolism, and survival. Dexmedetomidine also reduced neuronal apoptosis and oxidative stress by activating VDR expression, which involves neuronal function, inflammation, cell differentiation and immune regulation (Hou et al, 2020).…”

Regulation of Oxidative Stress by Long Non-Coding RNAs in Vascular Complications of Diabetes

“…Another study showed that MALAT1 competitively binds to miR-125b against vascular endothelial-cadherin, which may promote neovascularization in diabetic retinopathy [81]. Although there is a lack of direct evidence showing MALAT1/ miR-125b axis affects oxidative stress, it is reported that ROS production in neuronal PC12 cells is remarkably upregulated upon transfection with the miR-125b-5p mimic under high-glucose conditions [82]. Whether the interaction between MALAT1 and miR-125b contributes to the redox homeostasis in diabetic retinopathy is worthy of investigation.…”