Schwann cells apoptosis is induced by high glucose in diabetic peripheral neuropathy

Liu, Yu-pu; Shao, Shui-jin; Guo, Hai-dong

doi:10.1016/j.lfs.2020.117459

Cited by 83 publications

(56 citation statements)

References 172 publications

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“…The PI3K/AKT/mTOR pathway has also been revealed to be closely associated with autophagy ( 24 , 25 ). In addition, Liu et al ( 26 ) demonstrated that the PI3K/AKT signaling pathway was inhibited in a hyperglycemic environment, Autophagy-related circular RNA can attenuate autophagy and ROS production in Schwann cells subjected to hyperglycemia by promoting the activation of the PI3K/AKT/mTOR pathway ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

Yang

et al. 2021

Int J Mol Med

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Ischemic stroke is a leading cause of mortality and disability. diabetes mellitus, characterized by hyperglycemia, is a common concomitant disease of ischemic stroke, which is associated with autophagy dysfunction and blood-brain barrier (BBB) damage following cerebral ischemia/reperfusion (I/R) injury. At present, there is no effective treatment strategy for the disease. The purpose of the present study was to explore the molecular mechanisms underlying the protective effects of selenium on the BBB following I/R injury in hyperglycemic rats. Middle cerebral artery occlusion was performed in diabetic Sprague-dawley rats. Treatment with selenium and the autophagy inhibitor 3-methyladenine significantly reduced cerebral infarct volume, brain water content and Evans blue leakage, while increasing the expression of tight junction (TJ) proteins and decreasing that of autophagy-related proteins (P<0.05). In addition, selenium increased the phosphorylation levels of PI3K, AKT and mTOR (P<0.05). A mouse bEnd.3 brain microvascular endothelial cell line was co-cultured in vitro with an MA-h mouse astrocyte-hippocampal cell line to simulate the BBB. The cells were then subjected to hyperglycemia, followed by oxygen-glucose deprivation for 1 h and reoxygenation for 24 h. It was revealed that selenium increased TJ protein levels, reduced BBB permeability, decreased autophagy levels and enhanced the expression of phosphorylated (p)-AKT/AKT and p-mTOR/mTOR proteins (P<0.05). Treatment with wortmannin (an inhibitor of PI3K) significantly prevented the beneficial effects of selenium on the BBB, whereas insulin-like growth factor 1 (a PI3K activator) mimicked the effects of selenium. In conclusion, the present findings indicated that selenium can inhibit autophagy by regulating the PI3K/AKT/mTOR signaling pathway, significantly preventing BBB damage following cerebral I/R injury in hyperglycemic conditions.

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Section: Introductionmentioning

confidence: 99%

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

Yang

et al. 2021

Int J Mol Med

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“…Therefore, we still need to find more effective treatments. Although the pathogenesis of DPN is not fully understood, increasing evidence has shown that SC injury is one of the characteristics of DPN [8][9][10][11][12][13]. Oxidative stress induced by high glucose conditions in DM is a primary cause of tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…SCs ensheath all the axons of the peripheral nerves and secrete neurotrophic factors, which help maintain the structure and function of peripheral nerves [6,7]. Increasing evidence has shown that SCs serve an important role in DPN [8][9][10][11][12][13]. SC apoptosis induced by a high glucose environment is thought to be one of the primary causes of DPN.…”

Section: Introductionmentioning

confidence: 99%

Oltipraz Prevents High Glucose-Induced Oxidative Stress and Apoptosis in RSC96 Cells through the Nrf2/NQO1 Signalling Pathway

Jiang

Bian

et al. 2020

BioMed Research International

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Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). Schwann cell (SC) apoptosis contributes to the occurrence and development of DPN. Effective drugs to prevent SC apoptosis are required to relieve and reverse peripheral nerve injury caused by DM. Oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione], an agonist of nuclear factor erythroid derived-2-related factor 2 (Nrf2), exerts strong effect against oxidative stress in animal models or clinical patients in certain diseases, including heart failure, acute kidney injury, and liver injury. The aim of the present study was to determine the effectiveness of oltipraz in preventing SC apoptosis induced by high glucose levels. RSC96 cells pretreated with oltipraz were cultured in high-glucose medium (50 mM glucose) for 24 h, and cells cultured in medium containing 5 mM glucose were used as the control. Flow cytometry was used to evaluate the degree of apoptosis. A Cell Counting Kit-8 assay was used to assess cell viability. The mitochondrial membrane potential was assessed using JC-1 staining, and reactive oxygen species (ROS) generation was measured using 20,70-dichlorodihydrofluorescein diacetate staining. In addition, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) levels were also evaluated using the corresponding kits. Flow cytometry was subsequently used to detect apoptosis, and western blotting was used to measure the expression levels of nuclear factor erythroid derived-2-related factor 2 and NADPH quinone oxidoreductase 1. The results showed that high glucose concentration increased oxidative stress and apoptosis in RSC96 cells. Oltipraz improved cell viability and reduced apoptosis of RSC96 cells in the high glucose environment. Additionally, oltipraz exhibited a significant antioxidative effect, as shown by the decrease in MDA levels, increased SOD levels, and reduced ROS generation in RSC96 cells. The results of the present study suggest that oltipraz exhibits potential as an effective drug for treatment with DPN.

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“…Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus ( Feldman et al, 2017 ) complication and is the principal reason for amputation ( Feldman et al, 2017 ). Growing data have shown that Schwann cell dysfunction presents an essential role in DPN pathogenesis, such as slow migration speed, lipid metabolism abnormality, neurotrophy deficiency, and apoptosis ( Naruse, 2019 ; Liu et al, 2020 ). However, the molecular mechanisms of DPN progression are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

Liu

Bai

et al. 2021

Front. Mol. Biosci.

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Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

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Schwann cells apoptosis is induced by high glucose in diabetic peripheral neuropathy

Cited by 83 publications

References 172 publications

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

Oltipraz Prevents High Glucose-Induced Oxidative Stress and Apoptosis in RSC96 Cells through the Nrf2/NQO1 Signalling Pathway

Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

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