Affiliations 

  • 1 School of Medicine, University of Liverpool Liverpool L69 3BX, England, United Kingdom
  • 2 School of Health Science, International Medical University 57000 Kuala Lumpur, Malaysia
  • 3 Department of Applied Biomedical Science and Biotechnology, School of Health Science, International Medical University 57000 Kuala Lumpur, Malaysia
  • 4 School of Postgraduate, International Medical University 57000 Kuala Lumpur, Malaysia
  • 5 Department of Biotechnology, Faculty of Applied Sciences, UCSI University 56000 Cheras, Kuala Lumpur, Malaysia
Int J Biochem Mol Biol, 2023;14(3):25-31.
PMID: 37456910

Abstract

Diabetic neuropathy (DN) is a condition in which nerve fibers are continually exposed to high glucose-induced free radicals. Recent discoveries demonstrated that melatonin is an indole hormone that contributes to neuroprotection through the modulation of autophagy. Herein, this study aims to examine the neuroprotective effects of melatonin on Schwann cells under high glucose conditions. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay was used to measure cell viability. The activation of autophagosomes was determined using acridine orange staining (AO). Western blot assay was used to measure the expression of proteins involved in autophagy and endoplasmic reticulum (ER) stress. Our results demonstrated that melatonin at 1 µM has the highest protective effects on high glucose-induced cell death. Melatonin concentrations of 5 and 10 µM were found to be the most effective in reducing autophagy induced by high glucose. Under high glucose conditions, the protein expressions of LC3, ATF4, ATF6, CHOP, PERK and eIF2-α were up-regulated in Schwann cells. However, melatonin attenuated these changes by downregulating LC3 and the ER stress markers ATF4, ATF6, CHOP, PERK and eIF2-α protein expressions in Schwann cells. In conclusion, melatonin alleviates high glucose-induced autophagy in Schwann cells through PERK-eIF2α-ATF4-CHOP signaling pathways.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.