Alzheimer's β-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell line

被引:262
作者
Kawahara, M
Kuroda, Y
Arispe, N
Rojas, E
机构
[1] Univ Chile, Fac Med, Inst Biomed Sci, Santiago, Chile
[2] Tokyo Metropolitan Inst Neurosci, Dept Mol & Cellular Neurobiol, Fuchu, Tokyo 1838526, Japan
[3] Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20892 USA
关键词
D O I
10.1074/jbc.275.19.14077
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A growing number of reports suggest that elevated levels of extracellular Alzheimer's beta-amyloid protein alter the homeostasis of free [Ca2+](i) in different cell types of the mammalian brain. In line with these results, we have previously shown that A beta P[1-40] forms cation-selective channels (Ca2+ included) across artificial planar bilayers formed from acidic phospholipids and across excised membrane patches from immortalized hypothalamic GnRH neurons (GT1-7 cells), suggesting that the nonregulated Ca2+-influx through these spontaneously formed "amyloid channels" may provide a mechanism to explain its toxicity (1), We have now found and report here that the application of A beta P[1-40] to GT1-7 neurons consistently elevates [Ca2+](i) levels. We also found that human islet amylin and the prion protein fragment (PrP106-126), peptides that acquire beta-pleated sheet conformation in water solutions and have been reported to form ion channels across planar bilayer membranes, also increase cytosolic free calcium in GT1-7 neurons. Searching for protective agents, we found that soluble cholesterol, known to decrease the fluidity of the cell membrane, inhibits A beta P[1-40]-evoked [Ca2+](i) rise. These results suggest that unregulated Ca2+ entry across amyloid channels may be a common mechanism causing cell death, not only in diseases of the third age, including Alzheimer's disease and type 2 diabetes mellitus, but also in prion-induced diseases.
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页码:14077 / 14083
页数:7
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共 41 条
[11]   The formation of amphotericin B ion channels in lipid bilayers [J].
Fujii, G ;
Chang, JE ;
Coley, T ;
Steere, B .
BIOCHEMISTRY, 1997, 36 (16) :4959-4968
[12]   CELLULAR PROCESSING OF BETA-AMYLOID PRECURSOR PROTEIN AND THE GENESIS OF AMYLOID BETA-PEPTIDE [J].
HAASS, C ;
SELKOE, DJ .
CELL, 1993, 75 (06) :1039-1042
[13]   BOTH SPHINGOLIPIDS AND CHOLESTEROL PARTICIPATE IN THE DETERGENT INSOLUBILITY OF ALKALINE-PHOSPHATASE, A GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEIN, IN MAMMALIAN MEMBRANES [J].
HANADA, K ;
NISHIJIMA, M ;
AKAMATSU, Y ;
PAGANO, RE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (11) :6254-6260
[14]  
Ishiyama M, 1996, BIOL PHARM BULL, V19, P1518
[15]   CHEMISTRY AND OCCURRENCE OF SPHINGOLIPID LONG-CHAIN BASES [J].
KARLSSON, KA .
CHEMISTRY AND PHYSICS OF LIPIDS, 1970, 5 (01) :6-&
[16]   Alzheimer's disease amyloid beta-protein forms Zn2+-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons [J].
Kawahara, M ;
Arispe, N ;
Kuroda, Y ;
Rojas, E .
BIOPHYSICAL JOURNAL, 1997, 73 (01) :67-75
[17]   ALZHEIMERS-DISEASE - A CELL BIOLOGICAL PERSPECTIVE [J].
KOSIK, KS .
SCIENCE, 1992, 256 (5058) :780-783
[18]   INVIVO NEUROTOXICITY OF BETA-AMYLOID [BETA(1-40)] AND THE BETA(25-35) FRAGMENT [J].
KOWALL, NW ;
MCKEE, AC ;
YANKNER, BA ;
BEAL, MF .
NEUROBIOLOGY OF AGING, 1992, 13 (05) :537-542
[19]   GLUTAMATE-INDUCED INCREASE IN INTRACELLULAR CA-2+ CONCENTRATION IN ISOLATED HIPPOCAMPAL-NEURONS [J].
KUDO, Y ;
OGURA, A .
BRITISH JOURNAL OF PHARMACOLOGY, 1986, 89 (01) :191-198
[20]  
Lin MX, 1997, J BIOL CHEM, V272, P44