Bone marrow mesenchymal stem cells (MSCs) have been shown great potential for cardiac regeneration. However the therapeutic efficiency has become a major obstacle due to the poor survival of transplanted MSCs in ischemic cardiac tissue. Previous studies reported that melatonin could protect many different types of cells from apoptosis under various pathological conditions. In the present study, we demonstrated that melatonin, an endogenously secreted indoleamine had cytoprotection from hypoxia/serum deprivation (Hy/SD)-induced cell death in MSCs. We further investigated the possible mechanism and found out that melatonin attenuated (Hy/SD)-induced cell death could be via effectively reducing the generation of intracellular reactive oxygen species, an increase in the ratio of Bax/Bcl-2, loss of mitochondrial membrane potential and then activation of caspase-3 in MSCs in response to Hy/SD exposure. Furthermore, melatonin pretreatment significantly modulated the expression of phospho-P38MAPK and phospho-ERK1/2 in Hy/SD-induced MSCs and the protective effects of melatonin were partially reversed by ERK1/2 inhibitor but not p38 inhibitor, suggesting that melatonin inhibited Hy/SD-induced MSCs cell death through the MAPK signaling pathway in part. Taken together, the findings imply that melatonin could improve the survival of engrafted MSCs under hypoxia and serum deprivation condition. Our findings indicate that combination therapy with melatonin may provide therapeutic benefit for improving myocardial function after infarction.
Keywords: Apoptosis; CM-DCF (Pubchem CID: 77718); DAPI (Pubchem CID: 2954); DHE (Pubchem CID: 128682); ERK inhibitor PD98059 (Pubchem CID: 4713); Hypoxia/serum deprivation; JC-1 (Pubchem CID: 5492929); Melatonin; Melatonin (Pubchem CID: 896); Mesenchymal stem cell; Necrostatin-1 (Pubchem CID: 2828334); P38 inhibitor SB203580 (Pubchem CID: 176155); Propidium iodide (Pubchem CID: 104981); Thiazolyl blue tetrazolium bromide (Pubchem CID: 64965).
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