Heat-shock protein-27, -70 and peroxiredoxin-II show molecular chaperone function in sickle red cells: Evidence from transgenic sickle cell mouse model.

Abstract

Sickle cell disease (SCD) is an autosomal recessive genetic red cell disorder characterized by the production of a defective form of hemoglobin, hemoglobin-S, that is worldwide-distributed. The acute clinical manifestations of SCD are related to hemoglobin cyclic-polymerization and to the generation of rigid, dense red blood cells (RBCs). We studied RBCs membrane proteome from human sickle RBCs, fractioned according to density compared to normal RBCs. 2-DE followed by MS analysis was carried out. We identified 65 proteins differently expressed, divided into five major clusters according to their functions: (i) membrane-cytoskeleton proteins; (ii) metabolic enzymes; (iii) ubiquitin-proteasome-system; (iv) flotillins; (v) chaperones. HSP27, HSP70 and peroxiredoxin-II (Prx-II) showed the most relevant changes. They were differently recruited to sickle RBCs membrane in response to in vitro hypoxia. Potential markers were then validated in a transgenic-mouse model for SCD, the SAD mice, exposed to hypoxia mimicking acute SCD vaso-occlusive-crisis (VOCs); we found that HSP70 and HSP27 bound to RBCs membrane respectively after 12 h and 48 h of hypoxia, while Prx-II membrane binding was modulated during hypoxia. Our data indicate that HSP27 and HSP70 play a novel role as RBCs membrane protein protectors and as possibly new markers of severity of RBCs membrane damage during acute VOCs.

• Authors: Andrea Biondani, Franco Turrini, Franco Carta, Alessandro Matté, Alida Filippini, Angela Siciliano, Yves Beuzard, Lucia De Franceschi
• Journal: Proteomics. Clinical applications (Proteomics Clin Appl) Vol. 2 Issue 5 Pg. 706-19 (May 2008) ISSN: 1862-8346 [Print] Germany
• PMID: 21136868 (Publication Type: Journal Article)
• Copyright: Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.