The cycad neurotoxic amino acid, β-N-methylamino-L-alanine (BMAA), elevates intracellular calcium levels in dissociated rat brain cells

被引:65
作者
Brownson, DM
Mabry, TJ [1 ]
Leslie, SW
机构
[1] Univ Texas, Sch Biol Sci, Dept Bot, Austin, TX 78712 USA
[2] Univ Texas, Coll Pharm, Div Pharmacol & Toxicol, Austin, TX 78712 USA
[3] Univ Texas, Inst Neurosci, Austin, TX 78712 USA
关键词
beta-N-methylamino-L-alanine; excitatory amino acids; neurotoxicity; fura-2; dye; calcium; amyotrophic lateral sclerosis-parkinsonism; dementia complex; BMAA-carbamate;
D O I
10.1016/S0378-8741(02)00170-8
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Seeds of the Guam cycad Cycas micronesica K.D. Hill (Cycadaceae), which contain beta-methylamino-L-alanine (BMAA), have been implicated in the etiology of the devastating neurodisease ALS-PDC that is found among the native Chamorros on Guam. The disease also occurs in the native populations on Irian Jaya and the Kii Peninsula of Japan, and in all three areas the cycad seeds are used either dietarily or medically. ALS-PDC is a complex of amyotrophic lateral sclerosis and parkinsonism dementia complex with additional symptoms of Alzheimer's. It is well known that Ca2+ elevations in brain cells can lead to cell death and neurodiseases. Therefore, we evaluated the ability of the cycad toxin BMAA to elevate the intracellular calcium concentration ([Ca2+](i)) in dissociated newborn rat brain cells loaded with fura-2 dye. BMAA produced an increase in intracellular calcium levels in a concentration-dependent manner. The increases were dependent not only on extracellular calcium concentrations, but also significantly on the presence of bicarbonate ion. Increasing concentrations of sodium bicarbonate resulted in a potentiation of the BMAA-induced [Ca2+](i) elevation. The bicarbonate dependence did not result from the increased sodium concentration or alkalinization of the buffer. Our results support the hypothesis that the neurotoxicity of BMAA is due to an excitotoxic mechanism, involving elevated intracellular calcium levels and bicarbonate. Furthermore, since BMAA alone produced no increase in Ca2+ levels, these results suggest the involvement of a product of BMAA and CO2, namely a beta-carbamate, which has a structure similar to other excitatory amino acids (EAA) such as glutamate; thus, the causative agent for ALS-PDC on Guam and elsewhere may be the beta-carbamate of BMAA. These findings support the theory that some forms of other neurodiseases may also involve environmental toxins. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:159 / 167
页数:9
相关论文
共 56 条
[1]   THE NEUROTOXIN, BETA-N-METHYLAMINO-L-ALANINE (BMAA) INTERACTS WITH THE STRYCHNINE-INSENSITIVE GLYCINE MODULATORY SITE OF THE N-METHYL-D-ASPARTATE RECEPTOR [J].
ALLEN, CN ;
OMELCHENKO, I ;
ROSS, SM ;
SPENCER, P .
NEUROPHARMACOLOGY, 1995, 34 (06) :651-658
[2]   BETA-N-METHYLAMINO-L-ALANINE IN THE PRESENCE OF BICARBONATE IS AN AGONIST AT NON-N-METHYL-D-ASPARTATE-TYPE RECEPTORS [J].
ALLEN, CN ;
SPENCER, PS ;
CARPENTER, DO .
NEUROSCIENCE, 1993, 54 (03) :567-574
[3]   INOSITOL TRISPHOSPHATE AND CALCIUM SIGNALING [J].
BERRIDGE, MJ .
NATURE, 1993, 361 (6410) :315-325
[4]  
BRIDGES RJ, 1989, J NEUROSCI, V9, P2073
[5]  
Brown D., 1996, THESIS U TEXAS AUSTI, P1
[6]  
Brown E, 1993, J Laparoendosc Surg, V3, P13, DOI 10.1089/lps.1993.3.13
[7]  
CHA JHJ, 1990, P 20 ANN M AM SOC NE
[8]   GLUTAMATE NEUROTOXICITY AND DISEASES OF THE NERVOUS-SYSTEM [J].
CHOI, DW .
NEURON, 1988, 1 (08) :623-634
[9]  
CHOI DW, 1987, J NEUROSCI, V7, P369
[10]   INTERACTION BETWEEN BETA-N-METHYLAMINO-L-ALANINE AND EXCITATORY AMINO-ACID RECEPTORS IN BRAIN-SLICES AND NEURONAL CULTURES [J].
COPANI, A ;
CANONICO, PL ;
CATANIA, MV ;
ARONICA, E ;
BRUNO, V ;
RATTI, E ;
VANAMSTERDAM, FTM ;
GAVIRAGHI, G ;
NICOLETTI, F .
BRAIN RESEARCH, 1991, 558 (01) :79-86