Am J Clin Exp Immunol 2012;1(1):33-48

Original Article
Lipid-free apolipoprotein A-I exerts an antioxidative role against cell-free

Ruijuan Du*, Imelda Winarsih*, Bow Ho, Jeak Ling Ding

Department of Biological Sciences, 14 Science Drive 4, Singapore 117543; Department of Microbiology, 5 Science Drive
2, Singapore 117597.  *Equal contributors.

Received May 17, 2012; accepted May, 2012; Epub May, 2012; Published June 30, 2012

Abstract: Cell-free hemoglobin (Hb) resulting from hemolysis is redox-active. It disrupts the oxidoreducing
microenvironment, shifting the balance unfavorably towards tissue cytotoxicity. Thus, immediate suppression of the
Hb-redox activity and removal of the cell-free plasma Hb is vital for maintaining homeostasis and survival. Among several
known Hb-binding plasma proteins, haptoglobin (Hp) is the primary antioxidant of Hb. However, Hb-mediated oxidative
stress persists in the covalently bound Hb-Hp aggregates or when Hp is depleted during a severe hemolysis. We
therefore inquired whether there is an alternative anti-oxidative defense tactic in the blood. Here, we identified an
Hb-interactome in the plasma, constituting Hb, Hp and lipid-free apolipoprotein A-I (apoAI). We found that apoAI acts
rapidly as a secondary antioxidant to interact with Hb and quench the Hb-redox activity. We showed that apoAI either acts
independently or collaborates with Hp to downregulate Hb-redox activity. Following the association between apoAI and
Hb, the apoAI facilitates the uptake of Hb by interacting with a scavenger receptor class B type 1 (SR-BI) displayed on
macrophages and hepatocytes. Our findings suggest that apoAI mediates an efficient pathway for the elimination of
cytotoxic Hb redox activity. (AJCEI1205001).

Keywords: Antioxidant; apolipoprotein A-I; redox-active hemoglobin; scavenger receptor class B type 1 (SR-BI)

Address all correspondence to:
Dr. Jeak Ling Ding
Department of Biological Sciences
National University of Singapore
14 Science Drive 4, Singapore 117543
Tel: (65)  6516-2776, Fax: (65) 6779-2486
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