Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells

Abstract Methylglyoxal (MGO), a precursor of advanced glycation end products (AGEs), is regarded as a pivotal mediator of vascular damage in patients with diabetes. We have previously reported that MGO induces transcriptional changes compatible with p53 activation in cultured human endothelial cells...

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Autores principales:	Xinmiao Zhang, Angelica Rodriguez-Niño, Diego O. Pastene, Prama Pallavi, Jacob van den Born, Stephan J. L. Bakker, Bernhard K. Krämer, Benito A. Yard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6ec653575d044273a6fd2d3553d72164
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spelling	oai:doaj.org-article:6ec653575d044273a6fd2d3553d721642021-12-02T14:26:16ZMethylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells10.1038/s41598-021-87561-92045-2322https://doaj.org/article/6ec653575d044273a6fd2d3553d721642021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87561-9https://doaj.org/toc/2045-2322Abstract Methylglyoxal (MGO), a precursor of advanced glycation end products (AGEs), is regarded as a pivotal mediator of vascular damage in patients with diabetes. We have previously reported that MGO induces transcriptional changes compatible with p53 activation in cultured human endothelial cells. To further substantiate this finding and to explore the underlying mechanisms and possible consequences of p53 activation, we aimed (1) to provide direct evidence for p53 activation in MGO-treated human umbilical vein endothelial cells (HUVECs), (2) to assess putative mechanisms by which this occurs, (3) to analyze down-stream effects on mTOR and autophagy pathways, and (4) to assess the potential benefit of carnosine herein. Exposure of HUVECs to 800 µM of MGO for 5 h induced p53 phosphorylation. This was paralleled by an increase in TUNEL and γ-H2AX positive cells, indicative for DNA damage. Compatible with p53 activation, MGO treatment resulted in cell cycle arrest, inhibition of mTORC1 and induction of autophagy. Carnosine co-treatment did not counteract MGO-driven effects. In conclusion, our results demonstrate that MGO elicits DNA damage and p53 activation in HUVECs, resulting in modulation of downstream pathways, e.g. mTORC1.Xinmiao ZhangAngelica Rodriguez-NiñoDiego O. PastenePrama PallaviJacob van den BornStephan J. L. BakkerBernhard K. KrämerBenito A. YardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xinmiao Zhang Angelica Rodriguez-Niño Diego O. Pastene Prama Pallavi Jacob van den Born Stephan J. L. Bakker Bernhard K. Krämer Benito A. Yard Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells
description	Abstract Methylglyoxal (MGO), a precursor of advanced glycation end products (AGEs), is regarded as a pivotal mediator of vascular damage in patients with diabetes. We have previously reported that MGO induces transcriptional changes compatible with p53 activation in cultured human endothelial cells. To further substantiate this finding and to explore the underlying mechanisms and possible consequences of p53 activation, we aimed (1) to provide direct evidence for p53 activation in MGO-treated human umbilical vein endothelial cells (HUVECs), (2) to assess putative mechanisms by which this occurs, (3) to analyze down-stream effects on mTOR and autophagy pathways, and (4) to assess the potential benefit of carnosine herein. Exposure of HUVECs to 800 µM of MGO for 5 h induced p53 phosphorylation. This was paralleled by an increase in TUNEL and γ-H2AX positive cells, indicative for DNA damage. Compatible with p53 activation, MGO treatment resulted in cell cycle arrest, inhibition of mTORC1 and induction of autophagy. Carnosine co-treatment did not counteract MGO-driven effects. In conclusion, our results demonstrate that MGO elicits DNA damage and p53 activation in HUVECs, resulting in modulation of downstream pathways, e.g. mTORC1.
format	article
author	Xinmiao Zhang Angelica Rodriguez-Niño Diego O. Pastene Prama Pallavi Jacob van den Born Stephan J. L. Bakker Bernhard K. Krämer Benito A. Yard
author_facet	Xinmiao Zhang Angelica Rodriguez-Niño Diego O. Pastene Prama Pallavi Jacob van den Born Stephan J. L. Bakker Bernhard K. Krämer Benito A. Yard
author_sort	Xinmiao Zhang
title	Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells
title_short	Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells
title_full	Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells
title_fullStr	Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells
title_full_unstemmed	Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells
title_sort	methylglyoxal induces p53 activation and inhibits mtorc1 in human umbilical vein endothelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6ec653575d044273a6fd2d3553d72164
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Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells

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