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Melatonin Prevents Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis in High Glucose-Treated Schwann Cells via Upregulation of Bcl2, NF-κB, mTOR, Wnt Signalling Pathways

1
School of Postgraduate Studies, International Medical University, Kuala Lumpur 57000, Malaysia
2
School of Pharmacy, Monash University Malaysia, Selangor 47500, Malaysia
3
School of Health Science, International Medical University, Kuala Lumpur 57000, Malaysia
4
School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(7), 198; https://doi.org/10.3390/antiox8070198
Received: 29 April 2019 / Revised: 7 June 2019 / Accepted: 14 June 2019 / Published: 26 June 2019
(This article belongs to the Special Issue Mitochondria-Targeted Antioxidants)
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Abstract

Neuropathy is a complication that affects more than 50% of long-standing diabetic patients. One of the causes of diabetes neuropathy (DN) is the apoptosis of Schwann cells due to prolonged exposure to high glucose and build-up of oxidative stress. Melatonin is a hormone that has a known antioxidant property. In this study, we investigated the protective effect of melatonin on high glucose-induced Schwann cells’ apoptosis. Our results revealed that high glucose promoted apoptosis via mitochondrial-related oxidative stress and downregulated Bcl-2 family proteins in Schwann cells. In this signalling pathway, Bcl-2, Bcl-XL and Mcl-1 proteins were down-regulated while p-BAD and Puma proteins were up-regulated by high glucose treatment. Besides, we also proved that high glucose promoted apoptosis in Schwann cells through decreasing the p-NF-κB in the NF-κB signalling pathway. Key regulators of mTOR signalling pathway such as p-mTOR, Rictor and Raptor were also down-regulated after high glucose treatment. Additionally, high glucose treatment also decreased the Wnt signalling pathway downstream proteins (Wnt 5a/b, p-Lrp6 and Axin). Our results showed that melatonin treatment significantly inhibited high glucose-induced ROS generation, restored mitochondrial membrane potential and inhibited high glucose-induced apoptosis in Schwann cells. Furthermore, melatonin reversed the alterations of protein expression caused by high glucose treatment. Our results concluded that melatonin alleviates high glucose-induced apoptosis in Schwann cells through mitigating mitochondrial-related oxidative stress and the alterations of Bcl-2, NF-κB, mTOR and Wnt signalling pathways. View Full-Text
Keywords: melatonin; apoptosis; reactive oxygen species; mitochondrial; Bcl-2; NF-κB; mTOR; Wnt melatonin; apoptosis; reactive oxygen species; mitochondrial; Bcl-2; NF-κB; mTOR; Wnt
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Tiong, Y.L.; Ng, K.Y.; Koh, R.Y.; Ponnudurai, G.; Chye, S.M. Melatonin Prevents Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis in High Glucose-Treated Schwann Cells via Upregulation of Bcl2, NF-κB, mTOR, Wnt Signalling Pathways. Antioxidants 2019, 8, 198.

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