Biomaterial Database

Molecular mechanism of psychosine-induced cell death in human oligodendrocyte cell line. 2003

Ehtishamul Haq, and Shailendra Giri, and Inderjit Singh, and Avtar K Singh

Department of Pediatrics, Medical University of South Carolina, USA.

This study delineates the molecular mechanism underlying psychosine-induced oligodendroglial cell death. An immortalized human oligodendroglial cell line, MO3.13, was treated with exogenous psychosine (beta-galactosylsphingosine), a toxic metabolite that accumulates in the tissues of patients with Krabbe's disease. The mode of cell death induced by psychosine was found to be apoptotic, as revealed by different apoptotic markers viz., TUNEL, DNA fragmentation and caspase cleavage/activation. The action of psychosine was redox sensitive, as measured by changes in mitochondrial membrane potential (psidelta), and this effect of psychosine could be reversed by pre-treatment with the antioxidant molecules N-acetyl-l-cysteine or pro-cysteine. Psychosine directly affects the mitochondria as revealed by the activation of caspase 9 but not caspase 8. Up-regulation of the c-jun/c-jun N-terminal kinase pathway by psychosine leads to the induction of AP-1 and, at the same time, psychosine also down-regulates the lipopolysaccharide-induced NF-kappaB transactivation. These observations indicate that the mechanism of action of psychosine is, through the up-regulation of AP-1, a pro-apoptotic pathway as well as, through the down-regulation of the NF-kappaB pathway, an antiapoptotic pathway.

UI	MeSH Term	Description	Entries
D007965	Leukodystrophy, Globoid Cell	An autosomal recessive metabolic disorder caused by a deficiency of GALACTOSYLCERAMIDASE leading to intralysosomal accumulation of galactolipids such as GALACTOSYLCERAMIDES and PSYCHOSINE. It is characterized by demyelination associated with large multinucleated globoid cells, predominantly involving the white matter of the central nervous system. The loss of MYELIN disrupts normal conduction of nerve impulses.	Diffuse Globoid Body Sclerosis,Galactosylceramidase Deficiency Disease,Krabbe Disease,Classic Globoid Cell Leukodystrophy,Early-Onset Globoid Cell Leukodystrophy,GALC Deficiency,Galactocerebrosidase Deficiency,Galactosylceramide Lipidosis,Galactosylceramide beta-Galactosidase Deficiency,Galactosylceramide-beta-Galactosidase Deficiency Disease,Galactosylcerebrosidase Deficiency,Galactosylsphingosine Lipidosis,Globoid Body Sclerosis, Diffuse,Globoid Cell Leukodystrophy,Globoid Cell Leukoencephalopathy,Globoid Leukodystrophy,Infantile Globoid Cell Leukodystrophy,Krabbe Leukodystrophy,Krabbe's Disease,Krabbe's Leukodystrophy,Late-Onset Globoid Cell Leukodystrophy,Leukodystrophy, Globoid Cell, Classic,Leukodystrophy, Globoid Cell, Early-Onset,Leukodystrophy, Globoid Cell, Infantile,Leukodystrophy, Globoid Cell, Late-Onset,Psychosine Lipidosis,Cell Leukodystrophies, Globoid,Cell Leukodystrophy, Globoid,Cell Leukoencephalopathies, Globoid,Cell Leukoencephalopathy, Globoid,Deficiencies, GALC,Deficiencies, Galactocerebrosidase,Deficiencies, Galactosylceramide beta-Galactosidase,Deficiency Disease, Galactosylceramidase,Deficiency Disease, Galactosylceramide-beta-Galactosidase,Deficiency Diseases, Galactosylceramidase,Deficiency Diseases, Galactosylceramide-beta-Galactosidase,Deficiency, GALC,Deficiency, Galactocerebrosidase,Deficiency, Galactosylceramide beta-Galactosidase,Disease, Galactosylceramidase Deficiency,Disease, Galactosylceramide-beta-Galactosidase Deficiency,Diseases, Galactosylceramidase Deficiency,Diseases, Galactosylceramide-beta-Galactosidase Deficiency,Early Onset Globoid Cell Leukodystrophy,GALC Deficiencies,Galactocerebrosidase Deficiencies,Galactosylceramidase Deficiency Diseases,Galactosylceramide beta Galactosidase Deficiency,Galactosylceramide beta Galactosidase Deficiency Disease,Galactosylceramide beta-Galactosidase Deficiencies,Galactosylceramide-beta-Galactosidase Deficiency Diseases,Globoid Cell Leukodystrophies,Globoid Cell Leukoencephalopathies,Globoid Leukodystrophies,Krabbes Disease,Krabbes Leukodystrophy,Late Onset Globoid Cell Leukodystrophy,Leukodystrophies, Globoid,Leukodystrophies, Globoid Cell,Leukodystrophy, Globoid,Leukodystrophy, Krabbe,Leukodystrophy, Krabbe's,Leukoencephalopathies, Globoid Cell,Leukoencephalopathy, Globoid Cell,beta-Galactosidase Deficiencies, Galactosylceramide,beta-Galactosidase Deficiency, Galactosylceramide
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009836	Oligodendroglia	A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.	Interfascicular Oligodendroglia,Oligodendrocytes,Perineuronal Oligodendroglia,Perineuronal Satellite Oligodendroglia Cells,Perivascular Oligodendroglia,Satellite Cells, Perineuronal, Oligodendroglia,Perineuronal Satellite Oligodendrocytes,Interfascicular Oligodendroglias,Oligodendrocyte,Oligodendrocyte, Perineuronal Satellite,Oligodendrocytes, Perineuronal Satellite,Oligodendroglia, Interfascicular,Oligodendroglia, Perineuronal,Oligodendroglia, Perivascular,Perineuronal Satellite Oligodendrocyte,Satellite Oligodendrocyte, Perineuronal,Satellite Oligodendrocytes, Perineuronal
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D011609	Psychosine	An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the cerebroside.	Galactosylsphingosine,Sphingosine Galactoside,Galactoside, Sphingosine
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man