NR AGGF
AU Kawahara,M.; Kuroda,Y.; Arispe,N.; Rojas,E.
TI Alzheimer's beta-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell line
QU The Journal of Biological Chemistry 2000 May 12; 275(19): 14077-83
PT journal article
AB A growing number of reports suggest that elevated levels of extracellular Alzheimer's beta-amyloid protein alter the homeostasis of free [Ca(2+)](i) in different cell types of the mammalian brain. In line with these results, we have previously shown that AbetaP[1-40] forms cation-selective channels (Ca(2+) 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 Ca(2+)-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 AbetaP[1-40] to GT1-7 neurons consistently elevates [Ca(2+)](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 AbetaP[1-40]-evoked [Ca(2+)](i) rise. These results suggest that unregulated Ca(2+) 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.
MH Alzheimer Disease/metabolism; Amyloid/*metabolism; Amyloid beta-Protein/*metabolism; Calcium/*metabolism; Cell Line, Transformed; Cholesterol/metabolism; Gonadorelin/metabolism; Homeostasis; Human; Hypothalamus/cytology/*metabolism; Islets of Langerhans/*metabolism; Neurons/metabolism; Prions/*metabolism; Support, Non-U.S. Gov't
AD Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan.
SP englisch
PO USA
EA pdf-Datei und HTML-Version