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      Conditioned medium derived from human amniotic stem cells delays H 2O 2-induced premature senescence in human dermal fibroblasts

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          Abstract

          Stem cells derived from human amniotic membrane (hAM) are promising targets in regenerative medicine. A previous study focused on human amniotic stem cells in skin wound and scar-free healing. The present study aimed to investigate whether hydrogen peroxide (H 2O 2)-induced senescence of human dermal fibroblasts (hDFs) was influenced by the anti-aging effect of conditioned medium (CdM) derived from human amniotic stem cells. First, the biological function of two types of amniotic stem cells, namely human amniotic epithelial cells (hAECs) and human amniotic mesenchymal stem cells (hAMSCs), on hDFs was compared. The results of cell proliferation and wound healing assays showed that CdM promoted cell proliferation and migration. In addition, CdM from hAECs and hAMSCs significantly promoted proliferation of senescent hDFs induced by H 2O 2. These results indicated that CdM protects cells from damage caused by H 2O 2. Treatment with CdM decreased senescence-associated β-galactosidase activity and improved the entry of proliferating cells into the S phase. Simultaneously, it was found that CdM increased the activity of superoxide dismutase and catalase and decreased malondialdehyde by reducing H 2O 2-induced intracellular reactive oxygen species production. It was found that CdM downregulated H 2O 2-stimulated 8-hydroxydeoxy-guanosine and γ-H2AX levels and decreased the expression of the senescence-associated proteins p21 and p16. In conclusion, the findings indicated that the paracrine effects derived from human amniotic stem cells aided delaying oxidative stress-induced premature senescence.

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          gammaH2AX: a sensitive molecular marker of DNA damage and repair.

          L-J Mah, A. El-Osta, T Karagiannis (2010)
          Phosphorylation of the Ser-139 residue of the histone variant H2AX, forming gammaH2AX, is an early cellular response to the induction of DNA double-strand breaks. Detection of this phosphorylation event has emerged as a highly specific and sensitive molecular marker for monitoring DNA damage initiation and resolution. Further, analysis of gammaH2AX foci has numerous other applications including, but not limited to, cancer and aging research. Quantitation of gammaH2AX foci has also been applied as a useful tool for the evaluation of the efficacy of various developmental drugs, particularly, radiation modifying compounds. This review focuses on the current status of gammaH2AX as a marker of DNA damage and repair in the context of ionizing radiation. Although the emphasis is on gamma-radiation-induced gammaH2AX foci, the effects of other genotoxic insults including exposure to ultraviolet rays, oxidative stress and chemical agents are also discussed.
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            Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells.

            Johanna Flach, Sietske Bakker, Mary Mohrin … (2014)
            Haematopoietic stem cells (HSCs) self-renew for life, thereby making them one of the few blood cells that truly age. Paradoxically, although HSCs numerically expand with age, their functional activity declines over time, resulting in degraded blood production and impaired engraftment following transplantation. While many drivers of HSC ageing have been proposed, the reason why HSC function degrades with age remains unknown. Here we show that cycling old HSCs in mice have heightened levels of replication stress associated with cell cycle defects and chromosome gaps or breaks, which are due to decreased expression of mini-chromosome maintenance (MCM) helicase components and altered dynamics of DNA replication forks. Nonetheless, old HSCs survive replication unless confronted with a strong replication challenge, such as transplantation. Moreover, once old HSCs re-establish quiescence, residual replication stress on ribosomal DNA (rDNA) genes leads to the formation of nucleolar-associated γH2AX signals, which persist owing to ineffective H2AX dephosphorylation by mislocalized PP4c phosphatase rather than ongoing DNA damage. Persistent nucleolar γH2AX also acts as a histone modification marking the transcriptional silencing of rDNA genes and decreased ribosome biogenesis in quiescent old HSCs. Our results identify replication stress as a potent driver of functional decline in old HSCs, and highlight the MCM DNA helicase as a potential molecular target for rejuvenation therapies.
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              Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions.

              Thomas Kusch, Laurence Florens, W Hayes MacDonald … (2004)
              Phosphorylation of the human histone variant H2A.X and H2Av, its homolog in Drosophila melanogaster, occurs rapidly at sites of DNA double-strand breaks. Little is known about the function of this phosphorylation or its removal during DNA repair. Here, we demonstrate that the Drosophila Tip60 (dTip60) chromatin-remodeling complex acetylates nucleosomal phospho-H2Av and exchanges it with an unmodified H2Av. Both the histone acetyltransferase dTip60 as well as the adenosine triphosphatase Domino/p400 catalyze the exchange of phospho-H2Av. Thus, these data reveal a previously unknown mechanism for selective histone exchange that uses the concerted action of two distinct chromatin-remodeling enzymes within the same multiprotein complex.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Med
                Journal ID (iso-abbrev): Int. J. Mol. Med
                Journal ID (publisher-id): IJMM
                Title: International Journal of Molecular Medicine
                Publisher: D.A. Spandidos
                ISSN (Print): 1107-3756
                ISSN (Electronic): 1791-244X
                Publication date (Print): November 2019
                Publication date (Electronic): 20 September 2019
                Publication date PMC-release: 20 September 2019
                Volume: 44
                Issue: 5
                Pages: 1629-1640
                Affiliations
                [1 ]Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, Liaoning 110013
                [2 ]Shenyang Amnion Biological Engineering Technology Research and Development Center Limited Company, Shenyang, Liaoning 110629, P.R. China
                Author notes
                Correspondence to: Professor Xining Pang or Dr Feng Zhao, Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, 77 Puhe Street, Shenbei, Shenyang, Liaoning 110013, P.R. China, E-mail: pangxining@ 123456126.com , E-mail: unicorn.zhao@ 123456163.com
                Article
                Publisher ID: ijmm-44-05-1629
                DOI: 10.3892/ijmm.2019.4346
                PMC ID: 6777671
                PubMed ID: 31545472
                SO-VID: e5a0e908-4d0c-4af1-ab3e-5898adb83384
                Copyright © Copyright: © Pan et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 14 November 2018
                Date accepted : 08 July 2019
                Categories
                Subject: Articles

                Keywords: human amniotic epithelial cells,human amniotic mesenchymal stem cells,human dermal fibroblasts,hydrogen peroxide,senescence
                Data availability:
                Keywords: human amniotic epithelial cells, human amniotic mesenchymal stem cells, human dermal fibroblasts, hydrogen peroxide, senescence

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