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

被引:31
作者
Biondani, Andrea [1 ]
Turrini, Franco [2 ]
Carta, Franco
Matte, Alessandro [1 ]
Filippini, Alida [1 ]
Siciliano, Angela [1 ]
Beuzard, Yves [3 ]
De Franceschi, Lucia [1 ]
机构
[1] Univ Verona, Sect Internal Med, Dept Clin & Expt Med, I-37100 Verona, Italy
[2] Univ Turin, Med Chem Sect, Dept Genet Biol & Med Chem, Turin, Italy
[3] Hop St Louis, Inst Univ Hematol, Lab Therap Gen Hematopoiet, Paris, France
关键词
chaperones; dense sickle red cells; membrane oxidative damage;
D O I
10.1002/prca.200780058
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 vasoocclusive-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.
引用
收藏
页码:706 / 719
页数:14
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