Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells
<p>Abstract</p> <p>Background</p> <p>Various by-products of the cellular metabolism, such as reactive carbonyl species (RCS) are potentially harmful to cells and tissues, and play a role in many physiological and pathological processes. Among various RCS is the highly r...
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| Format: | Article |
| Language: | English |
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BMC
2012-03-01
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| Series: | Chemistry Central Journal |
| Online Access: | http://journal.chemistrycentral.com/content/6/1/18 |
| _version_ | 1819279919823192064 |
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| author | Larsen Simon Kassem Moustapha Rattan Suresh IS |
| author_facet | Larsen Simon Kassem Moustapha Rattan Suresh IS |
| author_sort | Larsen Simon |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Various by-products of the cellular metabolism, such as reactive carbonyl species (RCS) are potentially harmful to cells and tissues, and play a role in many physiological and pathological processes. Among various RCS is the highly reactive dicarbonyl glyoxal (GO), which is a natural physiological metabolite produced by the auto-oxidation of glucose, and can form covalent adducts known as advanced glycation endproducts (AGE). We have previously reported that GO accelerates ageing and causes premature senescence in normal human skin fibroblasts.</p> <p>Results</p> <p>Using a bone marrow-derived telomerase-immortalised mesenchymal stem cell line hMSC-TERT we have observed that an exposure of cells to 0.75 mM and 1 mM GO induces irreversible cellular senescence within 3 days. Induction of senescence in hMSC-TERT was demonstrated by a variety of markers, including characteristic cell morphology and enlargement, vacuolisation, multinucleation, induction of senescence associated β-galactosidase, cell cycle arrest, and increased levels of a cell cycle inhibitor p16. These changes were accompanied by increased extent of DNA breaks as measured by the comet assay, and increased levels of the AGE product, carboxymethyl-lysine (CML). Furthermore, the <it>in vitro </it>differentiation potential of hMSC-TERT to become functional osteoblasts was highly reduced in GO-treated stem cells, as determined by alkaline phosphatase (ALP) activity and mineralized matrix (MM) formation.</p> <p>Conclusions</p> <p>The results of our study imply that an imbalanced glucose metabolism can reduce the functioning ability of stem cells <it>in vivo </it>both during ageing and during stem cell-based therapeutic interventions.</p> |
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| format | Article |
| id | doaj.art-df14d5a1231c4423be90ee5fb1c35621 |
| institution | Directory Open Access Journal |
| issn | 1752-153X |
| language | English |
| last_indexed | 2024-12-24T00:35:33Z |
| publishDate | 2012-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Chemistry Central Journal |
| spelling | doaj.art-df14d5a1231c4423be90ee5fb1c356212022-12-21T17:24:05ZengBMCChemistry Central Journal1752-153X2012-03-01611810.1186/1752-153X-6-18Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cellsLarsen SimonKassem MoustaphaRattan Suresh IS<p>Abstract</p> <p>Background</p> <p>Various by-products of the cellular metabolism, such as reactive carbonyl species (RCS) are potentially harmful to cells and tissues, and play a role in many physiological and pathological processes. Among various RCS is the highly reactive dicarbonyl glyoxal (GO), which is a natural physiological metabolite produced by the auto-oxidation of glucose, and can form covalent adducts known as advanced glycation endproducts (AGE). We have previously reported that GO accelerates ageing and causes premature senescence in normal human skin fibroblasts.</p> <p>Results</p> <p>Using a bone marrow-derived telomerase-immortalised mesenchymal stem cell line hMSC-TERT we have observed that an exposure of cells to 0.75 mM and 1 mM GO induces irreversible cellular senescence within 3 days. Induction of senescence in hMSC-TERT was demonstrated by a variety of markers, including characteristic cell morphology and enlargement, vacuolisation, multinucleation, induction of senescence associated β-galactosidase, cell cycle arrest, and increased levels of a cell cycle inhibitor p16. These changes were accompanied by increased extent of DNA breaks as measured by the comet assay, and increased levels of the AGE product, carboxymethyl-lysine (CML). Furthermore, the <it>in vitro </it>differentiation potential of hMSC-TERT to become functional osteoblasts was highly reduced in GO-treated stem cells, as determined by alkaline phosphatase (ALP) activity and mineralized matrix (MM) formation.</p> <p>Conclusions</p> <p>The results of our study imply that an imbalanced glucose metabolism can reduce the functioning ability of stem cells <it>in vivo </it>both during ageing and during stem cell-based therapeutic interventions.</p>http://journal.chemistrycentral.com/content/6/1/18 |
| spellingShingle | Larsen Simon Kassem Moustapha Rattan Suresh IS Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells Chemistry Central Journal |
| title | Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells |
| title_full | Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells |
| title_fullStr | Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells |
| title_full_unstemmed | Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells |
| title_short | Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells |
| title_sort | glucose metabolite glyoxal induces senescence in telomerase immortalized human mesenchymal stem cells |
| url | http://journal.chemistrycentral.com/content/6/1/18 |
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