Cytoprotective effect of melatonin against hypoxia/serum deprivation-induced cell death of bone marrow mesenchymal stem cells in vitro.

Abstract:

: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.

journal_name

Eur J Pharmacol

authors

Wang F,Zhou H,Du Z,Chen X,Zhu F,Wang Z,Zhang Y,Lin L,Qian M,Zhang X,Li X,Hao A

doi

10.1016/j.ejphar.2014.09.033

subject

Has Abstract

pub_date

2015-02-05 00:00:00

pages

157-65

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(14)00689-X

journal_volume

748

pub_type

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