title: Decreased SIRT3 in aged human mesenchymal stromal/stem cells increases cellular susceptibility to oxidative stress.
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.
authors.affiliation: Department of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratories of Myocardial Ischemia Mechanism and Treatment, Harbin Medical University, Ministry of Education, Harbin, China.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Shao
authors.forename: Chong-Yi
authors.initials: CY
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Dong-Yang
authors.initials: DY
authors.lastname: Zhang
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Fu
authors.forename: Kai-Yu
authors.initials: KY
authors.lastname: Liu
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Jia
authors.forename: Bao-Dong
authors.initials: BD
authors.lastname: Xie
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Jiang
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
authors.forename: Hai
authors.initials: H
authors.lastname: Tian
mesh_terms: D000375:Aging; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D002374:Catalase / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000096:biosynthesis / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; C466093:SIRT3 protein, human; D056566:Sirtuin 3
keywords: SIRT3; ageing; antioxidants; mesenchymal stromal/stem cells; myocardium; oxidative stress