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) were en...

Full description

Saved in:
Bibliographic Details
Main Authors: Ting Wang, Shu-chong Mei, Rong Fu, Hua-quan Wang, Zong-hong Shao
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2014/439530
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832548086300278784
author Ting Wang
Shu-chong Mei
Rong Fu
Hua-quan Wang
Zong-hong Shao
author_facet Ting Wang
Shu-chong Mei
Rong Fu
Hua-quan Wang
Zong-hong Shao
author_sort Ting Wang
collection DOAJ
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 Article
id doaj-art-cb47df0bb421463aaf55b6019080a033
institution Kabale University
issn 2314-8861
2314-7156
language English
publishDate 2014-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-cb47df0bb421463aaf55b6019080a0332025-02-03T06:42:18ZengWileyJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/439530439530Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic AnemiaTing Wang0Shu-chong Mei1Rong Fu2Hua-quan Wang3Zong-hong Shao4Department of Hematology, General Hospital, Tianjin Medical University, 154 Anshandao, Heping, Tianjin 300052, ChinaDepartment of Hematology, General Hospital, Tianjin Medical University, 154 Anshandao, Heping, Tianjin 300052, ChinaDepartment of Hematology, General Hospital, Tianjin Medical University, 154 Anshandao, Heping, Tianjin 300052, ChinaDepartment of Hematology, General Hospital, Tianjin Medical University, 154 Anshandao, Heping, Tianjin 300052, ChinaDepartment of Hematology, General Hospital, Tianjin Medical University, 154 Anshandao, Heping, Tianjin 300052, ChinaAbnormal 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.http://dx.doi.org/10.1155/2014/439530
spellingShingle Ting Wang
Shu-chong Mei
Rong Fu
Hua-quan Wang
Zong-hong Shao
Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia
Journal of Immunology Research
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
url http://dx.doi.org/10.1155/2014/439530
work_keys_str_mv AT tingwang expressionofshelterincomponentpot1isassociatedwithdecreasedtelomerelengthandimmunityconditioninhumanswithsevereaplasticanemia
AT shuchongmei expressionofshelterincomponentpot1isassociatedwithdecreasedtelomerelengthandimmunityconditioninhumanswithsevereaplasticanemia
AT rongfu expressionofshelterincomponentpot1isassociatedwithdecreasedtelomerelengthandimmunityconditioninhumanswithsevereaplasticanemia
AT huaquanwang expressionofshelterincomponentpot1isassociatedwithdecreasedtelomerelengthandimmunityconditioninhumanswithsevereaplasticanemia
AT zonghongshao expressionofshelterincomponentpot1isassociatedwithdecreasedtelomerelengthandimmunityconditioninhumanswithsevereaplasticanemia