Melatonin activates ABCA1 via the BiP/NRF1 pathway to suppress high-cholesterol-induced apoptosis of mesenchymal stem cells

8Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: Retarded wound healing in patients with obesity contributes to a risk of complications associated with vascular insufficiency and oxidative stress. The high cholesterol levels of patients with obesity are associated with apoptosis of engrafted umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). Melatonin contributes to the prevention of cholesterol accumulation in patients with obesity via a mechanism that is poorly understood. We therefore investigated the regulatory mechanism of melatonin in cholesterol-induced apoptosis. Methods: The protective effects of melatonin on cholesterol-induced apoptosis were investigated in UCB-MSCs. We used a mouse model of induced obesity to show that melatonin treatment restored the survival rate of transplanted UCB-MSCs and their wound-healing capacity. The mean values of the treatment groups were compared with those of the control group using Student’s t test, and differences among three or more groups were analyzed using one-way analysis of variance with Dunnett’s multiple comparison test. Results: Melatonin treatment increased the expression of ATP-binding cassette subfamily A member 1 (ABCA1), which reduced cholesterol accumulation and cholesterol-induced apoptosis. The mouse skin wound healing model showed that melatonin treatment restored the survival rate of transplanted UCB-MSCs and the wound-healing capacity of obese mice. Melatonin inhibited the expression of binding immunoglobulin protein (BiP) through the regulation of MT2/Sp1-dependent microRNA-597-5p. Melatonin decreased the co-localization of BiP with nuclear factor erythroid 2-related factor 1 (NRF1), which resulted in increased ABCA1 expression. Conclusion: Melatonin induced the efflux of intracellular cholesterol through ABCA1 to decrease apoptosis of UCB-MSCs via an MT2-dependent BiP/NRF1 pathway.

References Powered by Scopus

Melatonin: A well-documented antioxidant with conditional pro-oxidant actions

699Citations
N/AReaders
Get full text

Stress-activated cap'n'collar transcription factors in aging and human disease

689Citations
N/AReaders
Get full text

Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: Dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains

526Citations
N/AReaders
Get full text

Cited by Powered by Scopus

A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis

29Citations
N/AReaders
Get full text

Melatonin and the Programming of Stem Cells

16Citations
N/AReaders
Get full text

Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway

13Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Kim, J. S., Jung, Y. H., Lee, H. J., Chae, C. W., Choi, G. E., Lim, J. R., … Han, H. J. (2021). Melatonin activates ABCA1 via the BiP/NRF1 pathway to suppress high-cholesterol-induced apoptosis of mesenchymal stem cells. Stem Cell Research and Therapy, 12(1). https://doi.org/10.1186/s13287-021-02181-4

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 3

38%

Researcher 3

38%

Professor / Associate Prof. 1

13%

Lecturer / Post doc 1

13%

Readers' Discipline

Tooltip

Medicine and Dentistry 6

67%

Biochemistry, Genetics and Molecular Bi... 3

33%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 11

Save time finding and organizing research with Mendeley

Sign up for free