IMM-H004, A NOVEL COUMARIN DERIVATIVE COMPOUND, PROTECTS AGAINST AMYLOID BETA-INDUCED NEUROTOXICITY THROUGH A MITOCHONDRIAL-DEPENDENT PATHWAY

被引：28

作者：

Song, X. Y. ^{[1
,2
]}

Hu, J. F. ^{[3
]}

Sun, M. N. ^{[2
,4
]}

Li, Z. P. ^{[1
,2
]}

Wu, D. H. ^{[1
,2
]}

Ji, H. J. ^{[1
,2
]}

Yuan, Y. H. ^{[1
,2
]}

Zhu, Z. X. ^{[1
,2
]}

Han, N. ^{[1
,2
]}

Liu, G. ^{[2
,4
]}

Chen, N. H. ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Dept Pharmacol, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Beijing 100050, Peoples R China

[4] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China

来源：

NEUROSCIENCE | 2013年 / 242卷

基金：

中国国家自然科学基金;

关键词：

IMM-H004; amyloid beta; neurotoxicity; apoptosis; mitochondrial-dependent pathway; Alzheimer's disease; 2 DISTINCT PATHWAYS; ALZHEIMERS-DISEASE; CELL-DEATH; CORTICAL-NEURONS; INDUCED APOPTOSIS; HYDROGEN-SULFIDE; OXIDATIVE STRESS; DNA-DAMAGE; PC12; CELLS; IN-VITRO;

D O I：

10.1016/j.neuroscience.2013.02.049

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We have investigated the effect of IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-2H-chromen-2-one), a coumarin derivative, on the amyloid beta (A beta)-induced neurotoxicity in primary culture cortical neurons and pheochromocytoma (PC12) cells. Our results showed that treatment with IMM-H004 markedly reduced the number of apoptotic cells after exposure to A beta(25-35) or A beta(1-42), determined by MTT, TUNEL staining and Flow cytometry. Further study indicated that IMM-H004 significantly inhibited An-induced cytotoxicity and apoptosis by reversing An-induced mitochondrial dysfunction, including MMP (mitochondrial membrane potential) decrease, reactive oxygen species production, and mitochondrial release of cytochrome c. IMM-H004 can regulate the interaction between Bax and BcI-2, decreased levels of p53 and active caspase-3 protein induced by A beta(25-35). Furthermore, IMM-H004 also reduced translocation of AIF (apoptosis-inducing factor) induced by A beta(25-35). These results demonstrated that IMM-H004 was capable of protecting neuronal cells from A beta-induced degeneration through a mitochondrial-dependent apoptotic pathway. The results of this study lend further credence to the notion that IMM-H004 is a 'multipotent therapeutic agrent' that reduces toxic levels of brain A beta, and holds the potential to protect neuronal mitochondrial function in Alzheimer's disease. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：28 / 38

页数：11

共 53 条

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