Global gene expression reveals an increase of HMGB1 and APEX1 proteins and their involvement in oxidative stress, apoptosis and inflammation pathways among beta‐thalassaemia intermedia and major phenotypes

Summary Beta‐thalassaemia (BT) is classified according to blood transfusion requirement as minor (BTMi), intermedia (BTI) and major (BTM). BTM is the most severe form, requiring regular transfusions while transfusion need is only occasional in BTI. Differential gene expression between patients has n...

Full description

Saved in:
Bibliographic Details
Published in:British journal of haematology Vol. 186; no. 4; pp. 608 - 619
Main Authors: Maia de Oliveira da Silva, João Pedro, Brugnerotto, Ana Flávia, S. Romanello, Karen, K. L. Teixeira, Karina, Lanaro, Carolina, S. Duarte, Adriana, G. L. Costa, Gustavo, da Silva Araújo, Aderson, C. Bezerra, Marcos André, de Farias Domingos, Igor, Pereira Martins, Diego A., Malavazi, Iran, F. Costa, Fernando, Cunha, Anderson F.
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01.08.2019
Subjects:
APEX1
Apoptosis
Beta‐thalassaemia
Blood diseases
Blood transfusion
Cell differentiation
Erythroid cells
Gene expression
haemolytic anaemia
Hematology
HMGB1
HMGB1 protein
Metabolic pathways
Mutation
Oxidative stress
Phenotypes
Reactive oxygen species
Thalassemia
Transcription
haemolytic anaemia
HMGB1
APEX1
Beta-thalassaemia
oxidative stress
ISSN:0007-1048, 1365-2141, 1365-2141
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Beta‐thalassaemia (BT) is classified according to blood transfusion requirement as minor (BTMi), intermedia (BTI) and major (BTM). BTM is the most severe form, requiring regular transfusions while transfusion need is only occasional in BTI. Differential gene expression between patients has not been assessed so far. Here, we evaluated the global gene expression profiles during differentiation of human erythroid cells of two patients carrying the same mutation [CD39, (C → T)], though displaying different phenotypes (BTI and BTM). Considering the role of reactive oxygen species (ROS) in the pathophysiology of thalassaemia, we focused on differentially expressed genes involved in metabolic pathways triggered by ROS, such as inflammation and apoptosis, and, from these, we selected the Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) and High Mobility Group Box1 (HMGB1) genes, whose role in BT is not well established. An in‐depth expression analysis of transcriptional and protein levels in patients carrying a range of mutations associated with BT phenotypes indicated that APEX1 was increased in both BTI and BTM. Furthermore, higher amounts of HMGB1 was found in the plasma of BTI patients. Our findings suggest that these proteins have important roles in BT and could represent new targets for further studies aiming to improve the management of the disease.
Bibliography:This work was supported by the São Paulo Research Foundation (FAPESP, grant number 2011/50358‐3). Fellowships were granted to KSR and JPMOS (from Coordination for the Improvement of Higher Education Personnel‐CAPES), to KKLT (from the Brazilian National Council for Scientific and Technological Development‐CNPq).
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:0007-1048
1365-2141
1365-2141
DOI:10.1111/bjh.16062