Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia
Abnormal telomere attrition has been found to be closely related to patients with SAA in recent years. To identify the incidence of telomere attrition in SAA patients and investigate the relationship of telomere length with clinical parameters, SAA patients (n = 27) and healthy controls (n = 15) wer...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033360/ https://www.ncbi.nlm.nih.gov/pubmed/24892036 http://dx.doi.org/10.1155/2014/439530 |
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author | Wang, Ting Mei, Shu-chong Fu, Rong Wang, Hua-quan Shao, Zong-hong |
author_facet | Wang, Ting Mei, Shu-chong Fu, Rong Wang, Hua-quan Shao, Zong-hong |
author_sort | Wang, Ting |
collection | PubMed |
description | Abnormal telomere attrition has been found to be closely related to patients with SAA in recent years. To identify the incidence of telomere attrition in SAA patients and investigate the relationship of telomere length with clinical parameters, SAA patients (n = 27) and healthy controls (n = 15) were enrolled in this study. Telomere length of PWBCs was significantly shorter in SAA patients than in controls. Analysis of gene expression of Shelterin complex revealed markedly low levels of POT1 expression in SAA groups relative to controls. No differences in the gene expression of the other Shelterin components—TRF1, TRF2, TIN2, TPP1, and RAP1—were identified. Addition of IFN-γ to culture media induced a similar fall in POT1 expression in bone marrow cells to that observed in cells cultured in the presence of SAA serum, suggesting IFN-γ is the agent responsible for this effect of SAA serum. Furthermore, ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were all found similarly increased in bone marrow cells exposed to SAA serum, TNF-α, or IFN-γ. In summary, SAA patients have short telomeres and decreased POT1 expression. TNF-α and IFN-γ are found at high concentrations in SAA patients and may be the effectors that trigger apoptosis through POT1 and ATR. |
format | Online Article Text |
id | pubmed-4033360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-40333602014-06-02 Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia Wang, Ting Mei, Shu-chong Fu, Rong Wang, Hua-quan Shao, Zong-hong J Immunol Res Research Article Abnormal telomere attrition has been found to be closely related to patients with SAA in recent years. To identify the incidence of telomere attrition in SAA patients and investigate the relationship of telomere length with clinical parameters, SAA patients (n = 27) and healthy controls (n = 15) were enrolled in this study. Telomere length of PWBCs was significantly shorter in SAA patients than in controls. Analysis of gene expression of Shelterin complex revealed markedly low levels of POT1 expression in SAA groups relative to controls. No differences in the gene expression of the other Shelterin components—TRF1, TRF2, TIN2, TPP1, and RAP1—were identified. Addition of IFN-γ to culture media induced a similar fall in POT1 expression in bone marrow cells to that observed in cells cultured in the presence of SAA serum, suggesting IFN-γ is the agent responsible for this effect of SAA serum. Furthermore, ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were all found similarly increased in bone marrow cells exposed to SAA serum, TNF-α, or IFN-γ. In summary, SAA patients have short telomeres and decreased POT1 expression. TNF-α and IFN-γ are found at high concentrations in SAA patients and may be the effectors that trigger apoptosis through POT1 and ATR. Hindawi Publishing Corporation 2014 2014-05-06 /pmc/articles/PMC4033360/ /pubmed/24892036 http://dx.doi.org/10.1155/2014/439530 Text en Copyright © 2014 Ting Wang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Ting Mei, Shu-chong Fu, Rong Wang, Hua-quan Shao, Zong-hong Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia |
title | Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia |
title_full | Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia |
title_fullStr | Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia |
title_full_unstemmed | Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia |
title_short | Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia |
title_sort | expression of shelterin component pot1 is associated with decreased telomere length and immunity condition in humans with severe aplastic anemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033360/ https://www.ncbi.nlm.nih.gov/pubmed/24892036 http://dx.doi.org/10.1155/2014/439530 |
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