The mechanism for heme to prevent Aβ1-40 aggregation and its cytotoxicity

被引：28

作者：

Bao, Qingui ^{[1
]}

Luo, Ying ^{[1
]}

Li, Wei ^{[1
]}

Sun, Xiaobo ^{[3
]}

Zhu, Cuiqing ^{[3
]}

Li, Pingwei ^{[4
]}

Huang, Zhong-Xian ^{[2
]}

Tan, Xiangshi ^{[1
,2
]}

机构：

[1] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China

[2] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China

[3] Fudan Univ, Shanghai Med Coll, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China

[4] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA

来源：

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2011年 / 16卷 / 05期

基金：

中国国家自然科学基金;

关键词：

A beta(1-40); beta-Amyloid aggregation; Heme; Cytotoxicity; Alzheimer's disease; AMYLOID-BETA-PROTEIN; ALZHEIMERS-DISEASE; A-BETA; OXIDATIVE STRESS; PEPTIDE; MITOCHONDRIAL; OLIGOMERS; DEFICIENCY; BINDS; PEROXIDASE;

D O I：

10.1007/s00775-011-0783-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：

The beta-amyloid peptide (A beta) aggregation in the brain, known as amyloid plaques, is a hallmark of Alzheimer's disease (AD). The aberrant interaction of Cu2+ ion with A beta potentiates AD by inducing A beta aggregation and generating neurotoxic reactive oxygen species (ROS). In this study, the biosynthesized recombinant A beta(1-40) was, for the first time, used to investigate the mechanism for heme to prevent A beta(1-40) aggregation and its cytotoxicity. Cell viability studies of SH-SY5Y cells and rat primary hippocampal neurons showed that exogenous heme can protect the cells by reducing cytotoxicity in the presence of Cu2+ and/or A beta(1-40). UV-vis spectroscopy, circular dichroism spectroscopy, and differential pulse voltammetry were applied to examine the interaction between heme and A beta(1-40). It was proven that a heme-A beta(1-40) complex is formed and can stabilize the alpha-helix structure of A beta(1-40) to inhibit A beta(1-40) aggregation. The heme-A beta(1-40) complex possesses peroxidase activity and it may catalyze the decomposition of H2O2, reduce the generation of ROS downstream, and ultimately protect the cells. These results indicated that exogenous heme is able to alleviate the cytotoxicity induced by A beta(1-40) and Cu2+. This information may be a foundation to develop a potential strategy to treat AD.

引用

页码：809 / 816

页数：8

共 42 条

[1] Amyloid-β peptide binds with heme to form a peroxidase:: Relationship to the cytopathologies of Alzheimer's disease [J].

Atamna, H ;

Boyle, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (09) :3381-3386

[2] A role for heme in Alzheimer's disease:: Heme binds amyloid β and has altered metabolism [J].

Atamna, H ;

Frey, WH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (30) :11153-11158

[3] Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging [J].

Atamna, H ;

Killilea, DW ;

Killilea, AN ;

Ames, BN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (23) :14807-14812

[4] Heme deficiency selectively interrupts assembly of mitochondrial complex IV in human fibroblasts - Relevance to aging [J].

Atamna, H ;

Liu, JK ;

Ames, BN .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) :48410-48416

[5] Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease [J].

Atamna, Ham ;

Frey, William H., II .

MITOCHONDRION, 2007, 7 (05) :297-310

[6]

Atamna H, 2006, J ALZHEIMERS DIS, V10, P255

[7] Human and rodent amyloid-β peptides differentially bind heme: Relevance to the human susceptibility to Alzheimer's disease [J].

Atamna, Hani ;

Frey, William H., II ;

Ko, Novie .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2009, 487 (01) :59-65

[8] A molecular switch in amyloid assembly:: Met35 and amyloid β-protein oligomerization [J].

Bitan, G ;

Tarus, B ;

Vollers, SS ;

Lashuel, HA ;

Condron, MM ;

Straub, JE ;

Teplow, DB .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (50) :15359-15365

[9] Copper, zinc, and the metallobiology of Alzheimer disease [J].

Bush, AI .

ALZHEIMER DISEASE & ASSOCIATED DISORDERS, 2003, 17 (03) :147-150

[10] Evidence that the β-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of Aβ by zinc [J].

Cuajungco, MP ;

Goldstein, LE ;

Nunomura, A ;

Smith, MA ;

Lim, JT ;

Atwood, CS ;

Huang, XD ;

Farrag, YW ;

Perry, G ;

Bush, AI .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (26) :19439-19442

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