Open AccessMelatonin protects mesenchymal stem cells from autophagy‐mediated death under ischaemic ER‐stress conditions by increasing prion protein expression
Author(s) -
Lee Jun Hee,
Yoon Yeo Min,
Han YongSeok,
Jung Seo Kyung,
Lee Sang Hun
Publication year - 2019
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12545
Subject(s) - melatonin , autophagy , mesenchymal stem cell , microbiology and biotechnology , programmed cell death , apoptosis , unfolded protein response , oxidative stress , downregulation and upregulation , endoplasmic reticulum , biology , chemistry , endocrinology , biochemistry , gene
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.