UBIQUINONE PROTECTS CULTURED NEURONS AGAINST SPONTANEOUS AND EXCITOTOXIN-INDUCED DEGENERATION

被引:69
作者
FAVIT, A [1 ]
NICOLETTI, F [1 ]
SCAPAGNINI, U [1 ]
CANONICO, PL [1 ]
机构
[1] UNIV PAVIA, SCH DENT, CHAIR PHARMACOL, I-27100 PAVIA, ITALY
关键词
UBIQUINONE; GLUTAMATE; CEREBELLAR NEURONS; NEUROTOXICITY;
D O I
10.1038/jcbfm.1992.88
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ubiquinone is an endogenous quinone with pharmacological actions mainly related to its antioxidant properties. Here we report that ubiquinone protects cultured cerebellar granule cells against glutamate-induced neurotoxicity. In control cultures at 9 days of maturation in vitro (DIV), a 30-min exposure to 100-mu-M glutamate induced neuronal degeneration, as reflected by the great percentage (>90%) of cells labeled with propidium iodide 24 h after the exposure. Glutamate-induced neuronal death was dramatically reduced in cultures treated daily with ubiquinone since the second DIV. In these cultures, glutamate failed to induce a "delayed" increase in the influx of Ca-45(2+) an established parameter of excitotoxicity. Similarly, repeated addition of ubiquinone attenuated in a concentration-dependent manner the age-dependent degeneration of granule cells that is due to the toxic action of the endogenous glutamate progressively released into the medium. These results suggest that ubiquinone may be a useful drug in the therapy of acute and chronic neurodegenerative diseases related to hyperactivity of excitatory amino acid neurotransmission.
引用
收藏
页码:638 / 645
页数:8
相关论文
共 34 条
[1]   CALCIUM ACCUMULATION BY GLUTAMATE RECEPTOR ACTIVATION IS INVOLVED IN HIPPOCAMPAL CELL-DAMAGE AFTER ISCHEMIA [J].
BENVENISTE, H ;
JORGENSEN, MB ;
DIEMER, NH ;
HANSEN, AJ .
ACTA NEUROLOGICA SCANDINAVICA, 1988, 78 (06) :529-536
[2]   THE PARTICIPATION OF COENZYME-Q IN FREE-RADICAL PRODUCTION AND ANTIOXIDATION [J].
BEYER, RE .
FREE RADICAL BIOLOGY AND MEDICINE, 1990, 8 (06) :545-565
[3]  
BOOTH RFG, 1982, BIOCHEM INT, V5, P151
[4]  
BRAUGHLER JM, 1987, J BIOL CHEM, V262, P10438
[5]   TRANSIENT FORMATION OF SUPEROXIDE RADICALS IN POLY-UNSATURATED FATTY ACID-INDUCED BRAIN-SWELLING [J].
CHAN, PH ;
FISHMAN, RA .
JOURNAL OF NEUROCHEMISTRY, 1980, 35 (04) :1004-1007
[6]  
CHOI DW, 1990, CEREBROVAS BRAIN MET, V2, P105
[7]   GLUTAMATE NEUROTOXICITY AND DISEASES OF THE NERVOUS-SYSTEM [J].
CHOI, DW .
NEURON, 1988, 1 (08) :623-634
[8]  
COLLINGRIDGE GL, 1989, PHARMACOL REV, V41, P143
[9]   MECHANISM OF KAINATE TOXICITY TO CEREBELLAR NEURONS INVITRO IS ANALOGOUS TO REPERFUSION TISSUE-INJURY [J].
DYKENS, JA ;
STERN, A ;
TRENKNER, E .
JOURNAL OF NEUROCHEMISTRY, 1987, 49 (04) :1222-1228
[10]   GANGLIOSIDES PREVENT GLUTAMATE AND KAINATE NEUROTOXICITY IN PRIMARY NEURONAL CULTURES OF NEONATAL RAT CEREBELLUM AND CORTEX [J].
FAVARON, M ;
MANEV, H ;
ALHO, H ;
BERTOLINO, M ;
FERRET, B ;
GUIDOTTI, A ;
COSTA, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (19) :7351-7355