Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells

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Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells. / Larsen, Simon Asbjørn; Kassem, Moustapha; Rattan, Suresh.

I: Chemistry Central Journal, Bind 6, Nr. 18, 17.03.2012, s. 6-18.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Larsen, Simon Asbjørn ; Kassem, Moustapha ; Rattan, Suresh. / Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells. I: Chemistry Central Journal. 2012 ; Bind 6, Nr. 18. s. 6-18.

Bibtex

@article{b6a448b9cb48487f82235a6c7704b40b,
title = "Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells",
abstract = "BackgroundVarious 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.ResultsUsing 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 beta-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 in vitro 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.ConclusionsThe results of our study imply that an imbalanced glucose metabolism can reduce the functioning ability of stem cells in vivo both during ageing and during stem cell-based therapeutic interventions.",
author = "Larsen, {Simon Asbj{\o}rn} and Moustapha Kassem and Suresh Rattan",
year = "2012",
month = "3",
day = "17",
doi = "10.1186/1752-153X-6-18",
language = "English",
volume = "6",
pages = "6--18",
journal = "Chemistry Central Journal",
issn = "1752-153X",
publisher = "BioMed Central Ltd.",
number = "18",

}

RIS

TY - JOUR

T1 - Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells

AU - Larsen, Simon Asbjørn

AU - Kassem, Moustapha

AU - Rattan, Suresh

PY - 2012/3/17

Y1 - 2012/3/17

N2 - BackgroundVarious 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.ResultsUsing 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 beta-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 in vitro 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.ConclusionsThe results of our study imply that an imbalanced glucose metabolism can reduce the functioning ability of stem cells in vivo both during ageing and during stem cell-based therapeutic interventions.

AB - BackgroundVarious 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.ResultsUsing 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 beta-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 in vitro 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.ConclusionsThe results of our study imply that an imbalanced glucose metabolism can reduce the functioning ability of stem cells in vivo both during ageing and during stem cell-based therapeutic interventions.

U2 - 10.1186/1752-153X-6-18

DO - 10.1186/1752-153X-6-18

M3 - Journal article

VL - 6

SP - 6

EP - 18

JO - Chemistry Central Journal

JF - Chemistry Central Journal

SN - 1752-153X

IS - 18

ER -