Pharmacoproteomics Profiling of Plasma From β-Thalassemia Patients in Response to Hydroxyurea Treatment
Zohaib M., Ansari S. H., Shamsi T. S., Zubarev R. A., Zarina S.
Journal of Clinical Pharmacology
Vol.59, Issue1, P. 98-106
Опубликовано: 2019
Тип ресурса: Статья
Аннотация:
β-Thalassemia is a genetic disorder caused by defects in the β-globin gene resulting in the absence or reduced synthesis of adult hemoglobin (HbA). Hydroxyurea is an effective drug to increase fetal γ-globin (HbF) expression, replacing the missing adult β-globin. The mechanism of HbF induction by hydroxyurea and improvement in clinical symptoms are still poorly understood. In the present study we performed comparative analysis of plasma proteome in pre– and post–hydroxyurea-treated β-thalassemia major transfusion-dependent children (n = 10, mean age = 3.2 years) as well as responders versus nonresponders to hydroxyurea treatment. Plasma was collected before and after 6 months of hydroxyurea treatment, with patients subcategorized on the basis of their response to hydroxyurea. Among 400 identified proteins using a label-free quantitative proteomics approach, 28 proteins were found to be significantly different in pre– versus post–hydroxyurea-treated groups, with transferrin receptor pro
Ключевые слова:
haptoglobin; hydroxyurea; quantitative proteomics; transferrin receptor protein; β-thalassemia
alpha 1 antitrypsin; apolipoprotein A; apolipoprotein C1; apolipoprotein L1; blood clotting factor 10; calgranulin A; carbonate dehydratase I; ceruloplasmin; complement component C4; ficolin; ficolin 3; haptoglobin; hemoglobin alpha chain; hemoglobin delta chain; hemoglobin F; hemoglobin gamma chain; hemopexin; hydroxyurea; immunoglobulin heavy chain; immunoglobulin heavy variable 3 72; immunoglobulin kappa chain; inter alpha trypsin inhibitor heavy chain h3; leucine rich repeat kinase 2; orosomucoid; peroxiredoxin 2; protein ambp; serum amyloid P; transferrin receptor; transferrin receptor protein 1; antisickling agent; hydroxyurea; protein; beta thalassemia; child; clinical article; comparative study; controlled study; drug mechanism; female; human; male; preschool child; protein expression; protein protein interaction; proteomics; quantitative analysis; reversed phase liquid chromatography; treatment duration; treatment response; upregulation; beta thalassemia; blood; clinical trial
Язык текста: Английский
ISSN: 1552-4604
Zohaib M.
Ansari S. H.
Shamsi T. S.
Zubarev R. A. Roman Aleksandrovich 1963-
Zarina S.
Зохаиб М.
Ансари С. Х.
Шамси Т. С.
Зубарев Р. А. Роман Александрович 1963-
Зарина С.
Pharmacoproteomics Profiling of Plasma From β-Thalassemia Patients in Response to Hydroxyurea Treatment
Текст визуальный непосредственный
Journal of Clinical Pharmacology
John Wiley & Sons, Inc.
Vol.59, Issue1 P. 98-106
2019
Статья
haptoglobin hydroxyurea quantitative proteomics transferrin receptor protein β-thalassemia
alpha 1 antitrypsin apolipoprotein A apolipoprotein C1 apolipoprotein L1 blood clotting factor 10 calgranulin A carbonate dehydratase I ceruloplasmin complement component C4 ficolin ficolin 3 haptoglobin hemoglobin alpha chain hemoglobin delta chain hemoglobin F hemoglobin gamma chain hemopexin hydroxyurea immunoglobulin heavy chain immunoglobulin heavy variable 3 72 immunoglobulin kappa chain inter alpha trypsin inhibitor heavy chain h3 leucine rich repeat kinase 2 orosomucoid peroxiredoxin 2 protein ambp serum amyloid P transferrin receptor transferrin receptor protein 1 antisickling agent hydroxyurea protein beta thalassemia child clinical article comparative study controlled study drug mechanism female human male preschool child protein expression protein protein interaction proteomics quantitative analysis reversed phase liquid chromatography treatment duration treatment response upregulation beta thalassemia blood clinical trial
β-Thalassemia is a genetic disorder caused by defects in the β-globin gene resulting in the absence or reduced synthesis of adult hemoglobin (HbA). Hydroxyurea is an effective drug to increase fetal γ-globin (HbF) expression, replacing the missing adult β-globin. The mechanism of HbF induction by hydroxyurea and improvement in clinical symptoms are still poorly understood. In the present study we performed comparative analysis of plasma proteome in pre– and post–hydroxyurea-treated β-thalassemia major transfusion-dependent children (n = 10, mean age = 3.2 years) as well as responders versus nonresponders to hydroxyurea treatment. Plasma was collected before and after 6 months of hydroxyurea treatment, with patients subcategorized on the basis of their response to hydroxyurea. Among 400 identified proteins using a label-free quantitative proteomics approach, 28 proteins were found to be significantly different in pre– versus post–hydroxyurea-treated groups, with transferrin receptor pro