Sirtuin3 protects aged human mesenchymal stem cells against oxidative stress and enhances efficacy of cell therapy for ischaemic heart diseases.

Abstract

Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was increased after SIRT3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3 silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and antioxidant enzymes Mn-superoxide dismutase (MnSOD) and catalase (CAT) increased in SIRT3-overexpressed O-hMSCs while they decreased in SIRT3-silenced Y-hMSCs after oxidative stress. Following myocardial infarction in adult rats in vivo, infarct size decreased and cardiac function was significantly enhanced after cell transplantation with SIRT3 overexpressed O-hMSCs. The number of apoptotic cells decreased and the survival rate of transplanted cells increased following SIRT3 overexpression in O-hMSCs. SIRT3 protects aged hMSCs against oxidative stress by positively regulating antioxidant enzymes (MnSOD and CAT) via increasing the expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.

• Authors: Dong-Yang Zhang, Chun-Feng Zhang, Bi-Cheng Fu, Lu Sun, Xue-Qing Wang, Wei Chen, Wei Liu, Kai-Yu Liu, Guo-Qing Du, Chong-Yi Ma, Shu-Lin Jiang, Ren-Ke Li, Hai Tian
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 22 Issue 11 Pg. 5504-5517 (11 2018) ISSN: 1582-4934 [Electronic] England
• PMID: 30091830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Antioxidants
• FOXO3 protein, human
• Forkhead Box Protein O3
• Protective Agents
• Reactive Oxygen Species
• Catalase
• Superoxide Dismutase
• superoxide dismutase 2
• SIRT3 protein, human
• Sirtuin 3

Topics

• Aging (genetics, pathology)
• Animals
• Antioxidants
• Bone Marrow (metabolism)
• Catalase (genetics)
• Cell- and Tissue-Based Therapy (methods)
• Forkhead Box Protein O3 (genetics)
• Gene Expression Regulation, Developmental
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (metabolism)
• Myocardial Infarction (genetics, pathology, therapy)
• Myocardial Ischemia (genetics, pathology, therapy)
• Oxidative Stress (genetics)
• Plasmids (genetics)
• Protective Agents
• Rats
• Reactive Oxygen Species
• Sirtuin 3 (administration & dosage, genetics)
• Superoxide Dismutase (genetics)
• Transfection