In:
Journal of Pineal Research, Wiley, Vol. 61, No. 1 ( 2016-08), p. 82-95
Abstract:
Melatonin, a hormone secreted by the pineal gland, possesses multiple biological activities such as antitumor, antioxidant, and anti‐ischemia. C‐kit + cardiac progenitor cells ( CPC s) have emerged as a promising tool for the treatment of heart diseases. However, the senescence of CPC s due to pathological stimuli leads to the decline of CPC s' functions and regenerative potential. This study was conducted to demonstrate whether melatonin antagonizes the senescence of CPC s in response to oxidative stress. Here, we found that the melatonin treatment markedly inhibited the senescent characteristics of CPC s after exposed to sublethal concentration of H 2 O 2 , including the increase in senescence‐associated β ‐galactosidase ( SA ‐ β ‐gal)‐positive CPC s, senescence‐associated heterochromatin loci ( SAHF ), secretory IL ‐6 level, and the upregulation of p53 and p21 proteins. Senescence‐associated proliferation reduction was also attenuated by melatonin in CPC s. Luzindole, the melatonin membrane receptor blocker, may block the melatonin‐mediated suppression of premature senescence in CPC s. Interestingly, we found that long noncoding RNA H19 and its derived miR‐675 were downregulated by H 2 O 2 in CPC s, but melatonin treatment could counter this alteration. Furthermore, knockdown of H19 or miR‐675 blocked antisenescence actions of melatonin on H 2 O 2 ‐treated CPC s. It was further verified that H19‐derived miR‐675 targeted at the 3′ UTR of USP 10, which resulted in the downregulation of p53 and p21 proteins. In summary, melatonin antagonized premature senescence of CPC s via H19/miR‐675/ USP 10 pathway, which provides new insights into pharmacological actions and potential applications of melatonin on the senescence of CPC s.
Type of Medium:
Online Resource
ISSN:
0742-3098
,
1600-079X
DOI:
10.1111/jpi.2016.61.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2027992-9
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