Brains of aged apolipoprotein E-deficient mice have increased levels of F2-isoprostanes, in vivo markers of lipid peroxidation

被引:50
作者
Praticò, D
Rokach, J
Tangirala, RK
机构
[1] Univ Penn, Sch Med, Stellar Chance Labs, Ctr Expt Therapeut,Dept Pharmacol, Philadelphia, PA 19104 USA
[2] Florida Inst Technol, Dept Chem, Melbourne, FL 32901 USA
关键词
apolipoprotein E-deficient mice; lipid peroxidation; isoprostanes;
D O I
10.1046/j.1471-4159.1999.0730736.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Apolipoprotein E (apoE) is the major apolipoprotein of the CNS, Differential expression of apoE isoforms has been linked to longevity and to the pathogenesis of Alzheimer's disease. Several studies have demonstrated that this glycoprotein is important in mature as well as in aging CNS, where it may serve neurotrophic and/or neuroprotective functions. Some reports have shown that apoE-deficient mice have age-dependent neurodegeneration and cognitive impairment; others have not confirmed these observations, ApoE-deficient mice also develop hypercholesterolemia on a chow diet and have in vivo increased plasma lipid peroxidation products. F-2-isoprostanes are prostaglandin F-2 alpha isomers and chemically stable peroxidation products of arachidonic acid. Both isoprostane F-2 alpha-III and isoprostane F-2 alpha-VI were markedly elevated in the brains of aged apoE-deficient mice compared with either wild-type C57 Bl/6 mice or a distinct mouse model of hypercholesterolemia, the low-density lipoprotein receptor-deficient mouse. By contrast, no difference in isoprostane levels was observed in young apoE-deficient mice compared with age-matched wild-type control mice. Our findings indicate that disorder of lipid metabolism in the absence of apoE can induce an age-dependent increase in brain lipid peroxidation products.
引用
收藏
页码:736 / 741
页数:6
相关论文
共 51 条
[21]   Oxidative stress hypothesis in Alzheimer's disease [J].
Markesbery, WR .
FREE RADICAL BIOLOGY AND MEDICINE, 1997, 23 (01) :134-147
[22]   Neurodegeneration and cognitive impairment in apoE-deficient mice is ameliorated by infusion of recombinant apoE [J].
Masliah, E ;
Samuel, W ;
Veinbergs, I ;
Mallory, M ;
Mante, M ;
Saitoh, T .
BRAIN RESEARCH, 1997, 751 (02) :307-314
[23]  
MASLIAH E, 1995, RESEARCH ADVANCES IN ALZHEIMER'S DISEASE AND RELATED DISORDERS, P405
[24]   NEURODEGENERATION IN THE CENTRAL-NERVOUS-SYSTEM OF APOE-DEFICIENT MICE [J].
MASLIAH, E ;
MALLORY, M ;
GE, NF ;
ALFORD, M ;
VEINBERGS, I ;
ROSES, AD .
EXPERIMENTAL NEUROLOGY, 1995, 136 (02) :107-122
[25]   Increased 3-nitrotyrosine in brains of Apo E-deficient mice [J].
Matthews, RT ;
Beal, MF .
BRAIN RESEARCH, 1996, 718 (1-2) :181-184
[26]   Phosphorylation of tau protein is not affected in mice lacking apolipoprotein E [J].
Mercken, L ;
Brion, JP .
NEUROREPORT, 1995, 6 (17) :2381-2384
[27]   Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides [J].
Miyata, M ;
Smith, JD .
NATURE GENETICS, 1996, 14 (01) :55-61
[28]   Cerebrospinal fluid F2-isoprostane levels are increased in Alzheimer's disease [J].
Montine, TJ ;
Markesbery, WR ;
Morrow, JD ;
Roberts, LJ .
ANNALS OF NEUROLOGY, 1998, 44 (03) :410-413
[29]   NON-CYCLOOXYGENASE-DERIVED PROSTANOIDS (F2-ISOPROSTANES) ARE FORMED INSITU ON PHOSPHOLIPIDS [J].
MORROW, JD ;
AWAD, JA ;
BOSS, HJ ;
BLAIR, IA ;
ROBERTS, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (22) :10721-10725
[30]   The isoprostanes - Current knowledge and directions for future research [J].
Morrow, JD ;
Roberts, LJ .
BIOCHEMICAL PHARMACOLOGY, 1996, 51 (01) :1-9