Analysis of protein profiling studies of β‐thalassemia/Hb E disease

Abstract

A number of studies have used global protein profiling technologies on a range of patient samples to detect proteins that are differentially expressed in β-thalassemia/Hb E as an aid for understanding the physiopathology of this disease. Seven studies have identified a total of 111 unique, differentially expressed proteins. Seven proteins (prothrombin, alpha-1-antichymotrypsin, fibrinogen beta chain, hemoglobin beta, selenium-binding protein, microtubule-actin cross-linking factor and adenomatous polyposis coli protein 2) have been identified in two independent studies, whereas two proteins (carbonic anhydrase 1 and peroxiredoxin-2) have been identified in three independent studies. Both of these latter two proteins were consistently upregulated in the studies that identified them. Ontological analysis of all differentially regulated proteins identified "response to inorganic substances" as the most significant functional annotation cluster, which is consistent with iron overload being a major pathological consequence of this disease. Despite the range of samples investigated and the relatively small number of studies undertaken, a coherent picture of the mediators of the pathological consequences of β-thalassemia/Hb E disease is starting to emerge.

Platelet proteome reveals specific proteins associated with platelet activation and the hypercoagulable state in β-thalassmia/HbE patients

“…This study, and the study by Karmakar 19 , only identified one protein in common, namely Hsp70. However, as reviewed elsewhere multiple studies determining the differences in proteomes between β-thalassemia/HbE patients and healthy volunteers rarely identify common proteins as a consequence of the usage of different samples sources (erythrocytes, platelet free plasma derived microparticles, plasma, etc) and different analysis methodologies, as extensively reviewed elsewhere 20 . In this regard we found higher serum ferritin levels in splenectomized patients than in non-splenectomized patients and healthy volunteers in contrast to the previous study 19 .…”

Proteomic Analysis of β-Thalassemia/HbE: A Perspective from Hematopoietic Stem Cells (HSCs)

“…Two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry or tandem mass spectrometry (MS and MS/MS) has been used for the investigation of β-thalassemic proteomes. The majority of differential expressed proteins between β-thalassemia patients and normal clinical specimens have been identified and characterized their functions in different metabolic processes in response to inorganic substances using an online DAVID gene ontological analysis [54]. Several enzymes in metabolic processes are usually abundant and easily found on the 2-DE, whereas low-abundant proteins involve in gene regulation and signal transduction cascades are difficult to detect.…”

“…In addition, PXD2 has function in stress response in the protective system during stress erythropoiesis in thalassemic mice model [61]. PXD2 is an abundant protein mostly identified in many proteomic studies from various clinical specimens of β-thalassemia [50,54,62]. An increased oxidative damage from alpha excess and iron overload thus triggers the cellular defensive mechanism, including antioxidative responses.…”

Spatial and Temporal Expression Characteristics of the HBB Gene Family in Six Different Pig Breeds

“…These gene alterations often cause either a decrease in β-globin synthesis or completely block synthesis [ 13 ]. For example, HbE/β-thalassemia is a G A substitution at the 26 position of the β-globin gene and replaces Glu with Lys, resulting in a decrease in the β-globin chain [ 14 , 15 , 16 , 17 ]. As such, 1–3% of the people in Southern China carry a β-thalassemia allele and over 20 β-thalassemia mutations have been reported in the Chinese population [ 18 ].…”