Shilpita Karmakar1, Debasis Banerjee2,3, Abhijit Chakrabarti4. 1. Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India. 2. Hematology Unit, Ramakrishna Mission Seva Prathisthan, Kolkata, India. 3. Clinical Haematology Service, Park Clinic, Kolkata, India. 4. Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India.
Abstract
PURPOSE: Thalassemias can be defined as a group with inherited hemolytic anemia due to differential expressions of α and β globin genes. Hemoglobin E combined with β thalassemia (HbEβ) creates high oxidative stress in platelets producing different degrees of pathophysiological severity. Numerous cases of thalassemia have been reported with thromboembolic complications due to the hypercoagulable state, the mechanism underlying that is not yet well understood. EXPERIMENTAL DESIGN: We have used 2DE and DIGE coupled with MALDI TOF/TOF-based MS identification and characterization of altered proteins in both splenectomized and nonsplenectomized HbEβ and β thalassemia to investigate the factors responsible for hypercoagulation. RESULTS: The study revealed elevated levels of chaperones like HSP70, protein disulfide isomerase; oxidative stress proteins like peroxiredoxin2 and superoxide dismutase1 along with high ROS levels. Upregulation of translation initiation factor 5a observed in thalassemia is a novel finding and plays a protective role toward cell survival under oxidative stress. CONCLUSIONS AND CLINICAL RELEVANCE: The altered levels of chaperones and oxidative stress proteins indicate toward regulation of integrin binding and platelet activation under oxidative stress. Altogether, this comparative proteomics study of platelets in thalassemia could provide an insight into better understanding of the pathophysiology of the disease.
PURPOSE:Thalassemias can be defined as a group with inherited hemolytic anemia due to differential expressions of α and β globin genes. Hemoglobin E combined with β thalassemia (HbEβ) creates high oxidative stress in platelets producing different degrees of pathophysiological severity. Numerous cases of thalassemia have been reported with thromboembolic complications due to the hypercoagulable state, the mechanism underlying that is not yet well understood. EXPERIMENTAL DESIGN: We have used 2DE and DIGE coupled with MALDI TOF/TOF-based MS identification and characterization of altered proteins in both splenectomized and nonsplenectomized HbEβ and β thalassemia to investigate the factors responsible for hypercoagulation. RESULTS: The study revealed elevated levels of chaperones like HSP70, protein disulfide isomerase; oxidative stress proteins like peroxiredoxin2 and superoxide dismutase1 along with high ROS levels. Upregulation of translation initiation factor 5a observed in thalassemia is a novel finding and plays a protective role toward cell survival under oxidative stress. CONCLUSIONS AND CLINICAL RELEVANCE: The altered levels of chaperones and oxidative stress proteins indicate toward regulation of integrin binding and platelet activation under oxidative stress. Altogether, this comparative proteomics study of platelets in thalassemia could provide an insight into better understanding of the pathophysiology of the disease.
Authors: Marta Lomnytska; Rui Pinto; Susanne Becker; Ulla Engström; Sonja Gustafsson; Christina Björklund; Markus Templin; Jan Bergstrand; Lei Xu; Jerker Widengren; Elisabeth Epstein; Bo Franzén; Gert Auer Journal: Biomark Res Date: 2018-01-12
Authors: Ingrid Pabinger; Maria Zellner; Lena Hell; Kristina Lurger; Lisa-Marie Mauracher; Ella Grilz; Christina Maria Reumiller; Georg Johannes Schmidt; Huriye Ercan; Silvia Koder; Alice Assinger; José Basilio; Johanna Gebhart; Cihan Ay Journal: Exp Mol Med Date: 2020-01-20 Impact factor: 8.718