Aberrant profiles of native and oxidized glypoproteins in Alzheimer plasma

被引:78
作者
Yu, HL
Chertkow, HM
Bergman, H
Schipper, HM
机构
[1] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Ctr Neurotranslat Res, Montreal, PQ H3T 1E2, Canada
[2] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Bloomfield Ctr Res Aging, Montreal, PQ H3T 1E2, Canada
[3] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada
[4] McGill Univ, Dept Geriatr Med, Montreal, PQ, Canada
关键词
Alzheimer disease; biomarkers; concanavalin A; glycoproteins; heparin; oxidative stress;
D O I
10.1002/pmic.200300475
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A proteomic approach was employed to elucidate possible differential expression of native and oxidized glycoproteins using pooled plasma samples derived from ten patients with sporadic Alzheimer's disease (AD) and pooled plasma samples from nine normal elderly control (NEC) subjects. The plasma samples were fractionated by sequential affinity chromatography on heparin-agarose (HepA) and concanavalin A-agarose (ConA) columns followed by separation on one-dimensional and two-dimensional polyacrylamide gels. Carbonylation (oxidation) of proteins was monitored by in-strip derivatization with 2,4-dinitrophenylhydrazine (DNP) and anti-DNP immunoblotting. Nine spots representing glycoproteins which showed enrichment or high specific oxidation indices in AD HepA-ConA 2-D gels relative to NEC samples were analyzed by matrix-assisted laser desorption-time of flight-mass spectrometry and identified with high probability (p < 0.001) as isoforms of human transferrin (Tf) hemopexin (Hpx) and alpha-1-antitrypsin (alpha-1-AT). These glycoproteins were concentrated, respectively, 5-, 6.5- and 107-fold in HepA-ConA eluates derived from AD plasma relative to the NEC samples. Specific oxidation indices of the identified Tf and Hpx isoforms in AD plasma were respectively, 7.4 and 2.8 relative to NEC. Our findings provide further evidence for systemic derangements in heme/iron/redox homeostasis and activation of the acute phase response in sporadic AD. Moreover, the data implicate isoforms of Tf, Hpx and alpha-1-AT as potential biological markers of this condition.
引用
收藏
页码:2240 / 2248
页数:9
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