Cargando…
The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells
In diabetic patients, the metabolism of excess glucose increases the toxicity of the aldehyde group of sugar. Aldehydes, including glyceraldehyde (GA), react with intracellular proteins to form advanced glycation end-products (AGEs), which deteriorate bone quality and cause osteoporosis. One of the...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912344/ https://www.ncbi.nlm.nih.gov/pubmed/35267965 http://dx.doi.org/10.3390/nu14050990 |
_version_ | 1784667099152515072 |
---|---|
author | Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi |
author_facet | Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi |
author_sort | Sakasai-Sakai, Akiko |
collection | PubMed |
description | In diabetic patients, the metabolism of excess glucose increases the toxicity of the aldehyde group of sugar. Aldehydes, including glyceraldehyde (GA), react with intracellular proteins to form advanced glycation end-products (AGEs), which deteriorate bone quality and cause osteoporosis. One of the causes of osteoporotic fractures is impaired osteoblast osteogenesis; however, the cytotoxic effects of aldehydes and the subsequent formation of AGEs in osteoblasts have not yet been examined in detail. Therefore, the present study investigated the cytotoxicity of intracellular GA and GA-derived AGEs, named toxic AGEs (TAGE), in the mouse osteoblastic cell line MC3T3-E1. Treatment with GA induced MC3T3-E1 cell death, which was accompanied by TAGE modifications in several intracellular proteins. Furthermore, the downregulated expression of Runx2, a transcription factor essential for osteoblast differentiation, and collagen correlated with the accumulation of TAGE. The GA treatment also reduced the normal protein levels of collagen in cells, suggesting that collagen may be modified by TAGE and form an abnormal structure. Collectively, the present results show for the first time that GA and TAGE exert cytotoxic effects in osteoblasts, inhibit osteoblastic differentiation, and decrease the amount of normal collagen. The suppression of GA production and associated accumulation of TAGE has potential as a novel therapeutic target for osteoporosis under hyperglycemic conditions. |
format | Online Article Text |
id | pubmed-8912344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89123442022-03-11 The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi Nutrients Article In diabetic patients, the metabolism of excess glucose increases the toxicity of the aldehyde group of sugar. Aldehydes, including glyceraldehyde (GA), react with intracellular proteins to form advanced glycation end-products (AGEs), which deteriorate bone quality and cause osteoporosis. One of the causes of osteoporotic fractures is impaired osteoblast osteogenesis; however, the cytotoxic effects of aldehydes and the subsequent formation of AGEs in osteoblasts have not yet been examined in detail. Therefore, the present study investigated the cytotoxicity of intracellular GA and GA-derived AGEs, named toxic AGEs (TAGE), in the mouse osteoblastic cell line MC3T3-E1. Treatment with GA induced MC3T3-E1 cell death, which was accompanied by TAGE modifications in several intracellular proteins. Furthermore, the downregulated expression of Runx2, a transcription factor essential for osteoblast differentiation, and collagen correlated with the accumulation of TAGE. The GA treatment also reduced the normal protein levels of collagen in cells, suggesting that collagen may be modified by TAGE and form an abnormal structure. Collectively, the present results show for the first time that GA and TAGE exert cytotoxic effects in osteoblasts, inhibit osteoblastic differentiation, and decrease the amount of normal collagen. The suppression of GA production and associated accumulation of TAGE has potential as a novel therapeutic target for osteoporosis under hyperglycemic conditions. MDPI 2022-02-26 /pmc/articles/PMC8912344/ /pubmed/35267965 http://dx.doi.org/10.3390/nu14050990 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells |
title | The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells |
title_full | The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells |
title_fullStr | The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells |
title_full_unstemmed | The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells |
title_short | The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells |
title_sort | association between accumulation of toxic advanced glycation end-products and cytotoxic effect in mc3t3-e1 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912344/ https://www.ncbi.nlm.nih.gov/pubmed/35267965 http://dx.doi.org/10.3390/nu14050990 |
work_keys_str_mv | AT sakasaisakaiakiko theassociationbetweenaccumulationoftoxicadvancedglycationendproductsandcytotoxiceffectinmc3t3e1cells AT takatatakanobu theassociationbetweenaccumulationoftoxicadvancedglycationendproductsandcytotoxiceffectinmc3t3e1cells AT takeuchimasayoshi theassociationbetweenaccumulationoftoxicadvancedglycationendproductsandcytotoxiceffectinmc3t3e1cells AT sakasaisakaiakiko associationbetweenaccumulationoftoxicadvancedglycationendproductsandcytotoxiceffectinmc3t3e1cells AT takatatakanobu associationbetweenaccumulationoftoxicadvancedglycationendproductsandcytotoxiceffectinmc3t3e1cells AT takeuchimasayoshi associationbetweenaccumulationoftoxicadvancedglycationendproductsandcytotoxiceffectinmc3t3e1cells |