IMM-H004, a novel coumarin derivative compound, protects against amyloid beta-induced neurotoxicity through a mitochondrial-dependent pathway. 2013

X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China.

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 (Aβ)-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 Aβ25-35 or Aβ1-42, determined by MTT, TUNEL staining and Flow cytometry. Further study indicated that IMM-H004 significantly inhibited Aβ-induced cytotoxicity and apoptosis by reversing Aβ-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 Bcl-2, decreased levels of p53 and active caspase-3 protein induced by Aβ25-35. Furthermore, IMM-H004 also reduced translocation of AIF (apoptosis-inducing factor) induced by Aβ25-35. These results demonstrated that IMM-H004 was capable of protecting neuronal cells from Aβ-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 Aβ, and holds the potential to protect neuronal mitochondrial function in Alzheimer's disease.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D003374 Coumarins Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid. 1,2-Benzopyrone Derivatives,1,2-Benzopyrones,Coumarin Derivative,Coumarine,1,2-Benzo-Pyrones,Benzopyran-2-ones,Coumarin Derivatives,Coumarines,1,2 Benzo Pyrones,1,2 Benzopyrone Derivatives,1,2 Benzopyrones,Benzopyran 2 ones,Derivative, Coumarin,Derivatives, 1,2-Benzopyrone,Derivatives, Coumarin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D016716 PC12 Cells A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation. Pheochromocytoma Cell Line,Cell Line, Pheochromocytoma,Cell Lines, Pheochromocytoma,PC12 Cell,Pheochromocytoma Cell Lines
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D045304 Cytochromes c Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV. Cytochrome c,Ferricytochrome c,Ferrocytochrome c,Apocytochrome C
D051033 Apoptosis Inducing Factor A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation. AIF Apoptosis Regulatory Protein,Apoptosis-Inducing Factor,Mitochondrial Apoptosis-Inducing Factor,Apoptosis-Inducing Factor, Mitochondrial,Mitochondrial Apoptosis Inducing Factor
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

Related Publications

X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
March 2015, CNS neuroscience & therapeutics,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
January 2014, European journal of pharmacology,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
August 2019, Neurotoxicity research,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
January 2019, Frontiers in bioscience (Elite edition),
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
January 2016, PloS one,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
August 2014, Journal of molecular neuroscience : MN,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
December 2020, Molecular biology reports,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
October 2012, Journal of neuroscience research,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
April 2019, International journal of molecular sciences,
X Y Song, and J F Hu, and M N Sun, and Z P Li, and D H Wu, and H J Ji, and Y H Yuan, and Z X Zhu, and N Han, and G Liu, and N H Chen
July 2015, CNS neuroscience & therapeutics,
Copied contents to your clipboard!