PMID:25210848

Citation	Wang, XQ, Shao, Y, Ma, CY, Chen, W, Sun, L, Liu, W, Zhang, DY, Fu, BC, Liu, KY, Jia, ZB, Xie, BD, Jiang, SL, Li, RK and Tian, H (2014) Decreased SIRT3 in aged human mesenchymal stromal/stem cells increases cellular susceptibility to oxidative stress. J. Cell. Mol. Med. 18:2298-310
Abstract	Sirtuin3 (SIRT3) is an important member of the sirtuin family of protein deacetylases that is localized to mitochondria and linked to lifespan extension in organisms ranging from yeast to humans. As aged cells have less regenerative capacity and are more susceptible to oxidative stress, we investigated the effect of ageing on SIRT3 levels and its correlation with antioxidant enzyme activities. Here, we show that severe oxidative stress reduces SIRT3 levels in young human mesenchymal stromal/stem cells (hMSCs). Overexpression of SIRT3 improved hMSCs resistance to the detrimental effects of oxidative stress. By activating manganese superoxide dismutase (MnSOD) and catalase (CAT), SIRT3 protects hMSCs from apoptosis under stress. SIRT3 expression, levels of MnSOD and CAT, as well as cell survival showed little difference in old versus young hMSCs under normal growth conditions, whereas older cells had a significantly reduced capacity to withstand oxidative stress compared to their younger counterparts. Expression of the short 28 kD SIRT3 isoform was higher, while the long 44 kD isoform expression was lower in young myocardial tissues compared with older ones. These results suggest that the active short isoform of SIRT3 protects hMSCs from oxidative injury by increasing the expression and activity of antioxidant enzymes. The expression of this short isoform decreases in cardiac tissue during ageing, leading to a reduced capacity for the heart to withstand oxidative stress.
Links	PubMed PMC4224562 Online version:10.1111/jcmm.12395
Keywords	Aging; Antioxidants/metabolism; Apoptosis/genetics; Catalase/genetics; Cell Line; Gene Expression Regulation; Humans; Mesenchymal Stromal Cells/metabolism; Mesenchymal Stromal Cells/pathology; Oxidative Stress/genetics; Reactive Oxygen Species/metabolism; Sirtuin 3/biosynthesis; Sirtuin 3/genetics; Superoxide Dismutase/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SIR3		GO:1902553: positive regulation of catalase activity	ECO:0000314:		P		Figure 2(H-I) shows that pSIRT3 transfection increases gene & protein levels of CAT. 2J indicates enzymatic activity of CAT is also enhanced.	complete CACAO 11337
HUMAN:SIR3		GO:1901671: positive regulation of superoxide dismutase activity	ECO:0000314:		P		Figure 2(E-F) shows that pSIRT3 transfection increases gene & protein levels of MnSOD. 2G indicates enzymatic activity of MnSOD is also enhanced.	complete CACAO 11338
HUMAN:SIR3		GO:1903206: negative regulation of hydrogen peroxide-induced cell death	ECO:0000316:	UniProtKB:P04040 UniProtKB:P04179	P		Figure 3J & 3K show that transfection with the SIRT3 expression construct significantly reduces hydrogen peroxide-induced apoptosis by enhancing antioxidant activity of CAT and MnSOD	complete CACAO 11339

References

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