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Melatonin protects mesenchymal stem cells from autophagy‐mediated death under ischaemic ER‐stress conditions by increasing prion protein expression

OBJECT: The purpose of this study was to explore whether melatonin could protect mesenchymal stem cells (MSCs) against ischaemic injury, by inhibiting endoplasmic reticulum (ER) stress and autophagy both in vivo and in vitro. MATERIALS AND METHODS: To confirm the protective effect of melatonin again...

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Detalles Bibliográficos
Autores principales: Lee, Jun Hee, Yoon, Yeo Min, Han, Yong‐Seok, Jung, Seo Kyung, Lee, Sang Hun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495509/
https://www.ncbi.nlm.nih.gov/pubmed/30430685
http://dx.doi.org/10.1111/cpr.12545
Descripción
Sumario:OBJECT: The purpose of this study was to explore whether melatonin could protect mesenchymal stem cells (MSCs) against ischaemic injury, by inhibiting endoplasmic reticulum (ER) stress and autophagy both in vivo and in vitro. MATERIALS AND METHODS: To confirm the protective effect of melatonin against ER stress in MSCs, markers of cell viability, apoptosis and autophagy were analysed. To further investigate the regenerative effect of melatonin‐treated MSCs in ischaemic tissues, a murine hindlimb ischaemic model was established. RESULTS: Under oxidative stress conditions, treatment with melatonin suppressed the activation of ER stress–associated proteins and autophagy‐associated proteins acting through upregulation of cellular prion protein (PrP(C)) expression. Consequently, inhibition of apoptotic cell death occurred. Melatonin also promoted the activation of MnSOD and catalase activities in MSCs. In a murine hindlimb ischaemia model, melatonin‐treated MSCs also enhanced the functional limb recovery as well as neovascularization. These beneficial effects of melatonin were all blocked by knock‐down of PrP(C) expression. CONCLUSION: Melatonin protects against ER stress/autophagy‐induced apoptotic cell death by augmenting PrP(C) expression. Thus, melatonin‐treated MSCs could be a potential cell‐based therapeutic agent for ER stress–induced ischaemic diseases, and melatonin‐induced PrP(C) might be a key molecule in ameliorating ER stress and autophagy.