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Chloroquine Interference with Hemoglobin Endocytic Trafficking Suppresses Adaptive Heme and Iron Homeostasis in Macrophages : The Paradox of an Antimalarial Agent
المؤلفون المشاركون
Vallelian, Florence
Schaer, Christian A.
Schoedon, Gabriele
Laczko, Endre
Schaer, Dominik J.
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2013، العدد 2013 (31 ديسمبر/كانون الأول 2013)، ص ص. 1-10، 10ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2013-06-11
دولة النشر
مصر
عدد الصفحات
10
التخصصات الرئيسية
العلوم الطبيعية والحياتية (متداخلة التخصصات)
الأحياء
الملخص EN
The CD163 scavenger receptor pathway for Hb:Hp complexes is an essential mechanism of protection against the toxicity of extracellular hemoglobin (Hb), which can accumulate in the vasculature and within tissues during hemolysis.
Chloroquine is a lysosomotropic agent, which has been extensively used as an antimalarial drug in the past, before parasite resistance started to limit its efficacy in most parts of the world.
More recent use of chloroquine is related to its immunomodulatory activity in patients with autoimmune diseases, which may also involve hemolytic disease components.
In this study we examined the effects of chloroquine on the human Hb clearance pathway.
For this purpose we developed a new mass-spectrometry-based method to specifically quantify intracellular Hb peptides within the endosomal-lysosomal compartment by single reaction monitoring (SRM).
We found that chloroquine exposure impairs trafficking of Hb:Hp complexes through the endosomal-lysosomal compartment after internalization by CD163.
Relative quantification of intracellular Hb peptides by SRM confirmed that chloroquine blocked cellular Hb:Hp catabolism.
This effect suppressed the cellular heme-oxygenase-1 (HO-1) response and shifted macrophage iron homeostasis towards inappropriately high expression of the transferrin receptor with concurrent inhibition of ferroportin expression.
A functional deficiency of Hb detoxification and heme-iron recycling may therefore be an adverse consequence of chloroquine treatment during hemolysis.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Schaer, Christian A.& Laczko, Endre& Schoedon, Gabriele& Schaer, Dominik J.& Vallelian, Florence. 2013. Chloroquine Interference with Hemoglobin Endocytic Trafficking Suppresses Adaptive Heme and Iron Homeostasis in Macrophages : The Paradox of an Antimalarial Agent. Oxidative Medicine and Cellular Longevity،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-504916
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Schaer, Christian A.…[et al.]. Chloroquine Interference with Hemoglobin Endocytic Trafficking Suppresses Adaptive Heme and Iron Homeostasis in Macrophages : The Paradox of an Antimalarial Agent. Oxidative Medicine and Cellular Longevity No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-504916
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Schaer, Christian A.& Laczko, Endre& Schoedon, Gabriele& Schaer, Dominik J.& Vallelian, Florence. Chloroquine Interference with Hemoglobin Endocytic Trafficking Suppresses Adaptive Heme and Iron Homeostasis in Macrophages : The Paradox of an Antimalarial Agent. Oxidative Medicine and Cellular Longevity. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-504916
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-504916
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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