Cargando…

Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate

Micro-vascularization is a fast, energy-dependent process that is compromised by elevated glucose concentrations such as in diabetes mellitus disease. Here, we studied the effect of the physiological bioinorganic polymer, polyphosphate (polyP), on the reduced ATP content and impaired function of end...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xiaohong, Ackermann, Maximilian, Neufurth, Meik, Wang, Shunfeng, Li, Qiang, Feng, Qingling, Schröder, Heinz C., Müller, Werner E. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418735/
https://www.ncbi.nlm.nih.gov/pubmed/30965879
http://dx.doi.org/10.3390/polym9110575
_version_ 1783403799731240960
author Wang, Xiaohong
Ackermann, Maximilian
Neufurth, Meik
Wang, Shunfeng
Li, Qiang
Feng, Qingling
Schröder, Heinz C.
Müller, Werner E. G.
author_facet Wang, Xiaohong
Ackermann, Maximilian
Neufurth, Meik
Wang, Shunfeng
Li, Qiang
Feng, Qingling
Schröder, Heinz C.
Müller, Werner E. G.
author_sort Wang, Xiaohong
collection PubMed
description Micro-vascularization is a fast, energy-dependent process that is compromised by elevated glucose concentrations such as in diabetes mellitus disease. Here, we studied the effect of the physiological bioinorganic polymer, polyphosphate (polyP), on the reduced ATP content and impaired function of endothelial cells cultivated under “high glucose” (35 mM diabetes mellitus conditions) concentrations. This high-energy biopolymer has been shown to provide a source of metabolic energy, stored in its phosphoanhydride bonds. We show that exposure of human umbilical vein endothelial cells (HUVEC cells) to “high glucose” levels results in reduced cell viability, increased apoptotic cell death, and a decline in intracellular ATP level. As a consequence, the ability of HUVEC cells to form tube-like structures in the in vitro cell tube formation assay was almost completely abolished under “high glucose” conditions. Those cells were grown onto a physiological collagen scaffold (collagen/basement membrane extract). We demonstrate that these adverse effects of increased glucose levels can be reversed by administration of polyP to almost normal values. Using Na-polyP, complexed in a stoichiometric (molar) ratio to Ca(2+) ions and in the physiological concentration range between 30 and 300 µM, an almost complete restoration of the reduced ATP pool of cells exposed to “high glucose” was found, as well as a normalization of the number of apoptotic cells and energy-dependent tube formation. It is concluded that the adverse effects on endothelial cells caused by the metabolic energy imbalance at elevated glucose concentrations can be counterbalanced by polyP, potentially opening new strategies for treatment of the micro-vascular complications in diabetic patients.
format Online
Article
Text
id pubmed-6418735
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64187352019-04-02 Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate Wang, Xiaohong Ackermann, Maximilian Neufurth, Meik Wang, Shunfeng Li, Qiang Feng, Qingling Schröder, Heinz C. Müller, Werner E. G. Polymers (Basel) Article Micro-vascularization is a fast, energy-dependent process that is compromised by elevated glucose concentrations such as in diabetes mellitus disease. Here, we studied the effect of the physiological bioinorganic polymer, polyphosphate (polyP), on the reduced ATP content and impaired function of endothelial cells cultivated under “high glucose” (35 mM diabetes mellitus conditions) concentrations. This high-energy biopolymer has been shown to provide a source of metabolic energy, stored in its phosphoanhydride bonds. We show that exposure of human umbilical vein endothelial cells (HUVEC cells) to “high glucose” levels results in reduced cell viability, increased apoptotic cell death, and a decline in intracellular ATP level. As a consequence, the ability of HUVEC cells to form tube-like structures in the in vitro cell tube formation assay was almost completely abolished under “high glucose” conditions. Those cells were grown onto a physiological collagen scaffold (collagen/basement membrane extract). We demonstrate that these adverse effects of increased glucose levels can be reversed by administration of polyP to almost normal values. Using Na-polyP, complexed in a stoichiometric (molar) ratio to Ca(2+) ions and in the physiological concentration range between 30 and 300 µM, an almost complete restoration of the reduced ATP pool of cells exposed to “high glucose” was found, as well as a normalization of the number of apoptotic cells and energy-dependent tube formation. It is concluded that the adverse effects on endothelial cells caused by the metabolic energy imbalance at elevated glucose concentrations can be counterbalanced by polyP, potentially opening new strategies for treatment of the micro-vascular complications in diabetic patients. MDPI 2017-11-04 /pmc/articles/PMC6418735/ /pubmed/30965879 http://dx.doi.org/10.3390/polym9110575 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Xiaohong
Ackermann, Maximilian
Neufurth, Meik
Wang, Shunfeng
Li, Qiang
Feng, Qingling
Schröder, Heinz C.
Müller, Werner E. G.
Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate
title Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate
title_full Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate
title_fullStr Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate
title_full_unstemmed Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate
title_short Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate
title_sort restoration of impaired metabolic energy balance (atp pool) and tube formation potential of endothelial cells under “high glucose”, diabetic conditions by the bioinorganic polymer polyphosphate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418735/
https://www.ncbi.nlm.nih.gov/pubmed/30965879
http://dx.doi.org/10.3390/polym9110575
work_keys_str_mv AT wangxiaohong restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate
AT ackermannmaximilian restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate
AT neufurthmeik restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate
AT wangshunfeng restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate
AT liqiang restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate
AT fengqingling restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate
AT schroderheinzc restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate
AT mullerwernereg restorationofimpairedmetabolicenergybalanceatppoolandtubeformationpotentialofendothelialcellsunderhighglucosediabeticconditionsbythebioinorganicpolymerpolyphosphate