Protective effects of fangchinoline and tetrandrine on hydrogen peroxide-induced oxidative neuronal cell damage in cultured rat cerebellar granule cells

被引:7
作者
Koh, SB
Ban, JY
Lee, BY
Seong, YH
机构
[1] Chungbuk Natl Univ, Coll Vet Med, Cheongju 361763, Chungbuk, South Korea
[2] Chungbuk Natl Univ, Vet Med Res Inst, Cheongju 361763, Chungbuk, South Korea
关键词
fangchinoline; tetrandrine; H2O2; neurotoxicity; cytosolic free Ca2+ concentration; cerebellar granule cells;
D O I
暂无
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
The present study was performed to examine the neuroprotective effects of fangchinoline (FAN) and tetrandrine (TET), bisbenzylisoquinoline alkaloids, which exhibit the characteristics of Ca2+ channel blockers, on H2O2-induced neurotoxicity using cultured rat cerebellar granule neurons. H2O2 produced a concentration-dependent reduction of cell viability, which was blocked by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, verapamil, an L-type Ca2+ channel blocker, and N-G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Pretreatment with FAN and TET over a concentration range of 0.1 to 10 muM significantly decreased the H2O2-induced neuronal cell death as assessed by a trypan blue exclusion test, a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and the number of apoptotic nuclei. In addition, FAN and TET inhibited the H2O2-induced elevation of glutamate release into the medium, elevation of the cytosolic free Ca2+ concentration ([Ca2+](c)), and generation of reactive oxygen species (ROS). These results suggest that FAN and TET may mitigate the harmful effects of H2O2-induced neuronal cell death by interfering with the increase of [Ca2+](C), and then by inhibiting glutamate release and generation of ROS.
引用
收藏
页码:506 / 512
页数:7
相关论文
共 24 条
[1]  
Baltrons MA, 1997, J NEUROSCI RES, V49, P333
[2]   THE SUPEROXIDE-FORMING ENZYMATIC SYSTEM OF PHAGOCYTES [J].
BELLAVITE, P .
FREE RADICAL BIOLOGY AND MEDICINE, 1988, 4 (04) :225-261
[3]   CHARACTERIZATION OF THE CELLULAR REDUCTION OF 3-(4,5-DIMETHYLTHIAZOL-2-YL)-2,5-DIPHENYLTETRAZOLIUM BROMIDE (MTT) - SUBCELLULAR-LOCALIZATION, SUBSTRATE DEPENDENCE, AND INVOLVEMENT OF MITOCHONDRIAL ELECTRON-TRANSPORT IN MTT REDUCTION [J].
BERRIDGE, MV ;
TAN, AS .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1993, 303 (02) :474-482
[4]   Protective effect of fangchinoline on cyanide-induced neurotoxicity in cultured rat cerebellar granule cells [J].
Cho, SO ;
Seong, YH .
ARCHIVES OF PHARMACAL RESEARCH, 2002, 25 (03) :349-356
[5]   OXIDATIVE STRESS, GLUTAMATE, AND NEURODEGENERATIVE DISORDERS [J].
COYLE, JT ;
PUTTFARCKEN, P .
SCIENCE, 1993, 262 (5134) :689-695
[6]  
Duffy S, 1996, J NEUROSCI, V16, P71
[7]   AMINO-ACID NEUROTRANSMITTERS IN POSTMORTEM HUMAN-BRAIN ANALYZED BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION [J].
ELLISON, DW ;
BEAL, MF ;
MARTIN, JB .
JOURNAL OF NEUROSCIENCE METHODS, 1987, 19 (04) :305-315
[8]   Apoptotic vs nonapoptotic cytotoxicity induced by hydrogen peroxide [J].
Gardner, AM ;
Xu, FH ;
Fady, C ;
Jacoby, FJ ;
Duffey, DC ;
Tu, YP ;
Lichtenstein, A .
FREE RADICAL BIOLOGY AND MEDICINE, 1997, 22 (1-2) :73-83
[9]   BIOLOGICALLY RELEVANT METAL ION-DEPENDENT HYDROXYL RADICAL GENERATION - AN UPDATE [J].
HALLIWELL, B ;
GUTTERIDGE, JMC .
FEBS LETTERS, 1992, 307 (01) :108-112
[10]   REACTIVE OXYGEN SPECIES AND THE CENTRAL-NERVOUS-SYSTEM [J].
HALLIWELL, B .
JOURNAL OF NEUROCHEMISTRY, 1992, 59 (05) :1609-1623