5-methoxytryptophan protects MSCs from stress induced premature senescence by upregulating FoxO3a and mTOR.

ABSTRACT: 5-methoxytryptophan (5-MTP) is a newly discovered tryptophan metabolite which controls stress-induced inflammatory signals. To determine whether 5-MTP protects against stress-induced mesenchymal stem cell (MSC) senescence, we incubated bone marrow-derived MSC (BM-MSC) in high-glucose medium or regular medium for 2 weeks followed by addiction of 5-MTP (10 μM) or vehicle for 48 h. 5-MTP reduced p16 and p21 expression, senescence-associated β-Gal (SA-β-Gal) and IL-6 secretion and increased BrdU incorporation. 5-MTP exerted a similar effect on BM-MSC senescence induced by a sublethal concentration of H₂O₂. 5-MTP enhanced FoxO3a expression and increased superoxide dismutase and catalase activities in HG BM-MSCs. Silencing of FoxO3a with siRNA abrogated 5-MTP-mediated reduc

SUBMITTER: Chang TC 

PROVIDER: S-EPMC5593915 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature