NR ALQM
AU Thellung,S.; Florio,T.; Villa,V.; Corsaro,A.; Arena,S.; Amico,C.; Robello,M.; Salmona,M.; Forloni,G.; Bugiani,O.; Tagliavini,F.; Schettini,G.
TI Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in rat cerebellar granule cells treated with the prion protein fragment 106-126
QU Neurobiology of Disease 2000 Aug; 7(4): 299-309
PT journal article
AB Prion diseases are neurodegenerative pathologies characterized by the accumulation, in the brain, of altered forms of the prion protein (PrP), named PrPsc. A synthetic peptide homologous to residues 106-126 of PrP (PrP106-126) was reported to maintain the neurodegenerative characteristics of PrPsc. We investigated the intracellular mechanisms involved in PrP106-126-dependent degeneration of primary cultures of cerebellar granule neurons. Prolonged exposure of such neurons to PrP106-126 induced apoptotic cell death. The L-type voltage-sensitive calcium channel blocker nicardipine reproduced this effect, suggesting that blockade of Ca(2+) entry through this class of calcium channels may be responsible for the granule cell degeneration. Microfluorometric analysis showed that PrP106-126 caused a reduction in cytosolic calcium levels, elicited by depolarizing K(+) concentrations in these neurons. Electrophysiological studies demonstrated that PrP106-126 and nicardipine selectively reduce the L-type calcium channel current. These data demonstrate that PrP106-126 alters the activity of L-type voltage-sensitive calcium channels in rat cerebellar granule cells and suggest that this phenomenon is related to the cell death induced by the peptide.
MH Animal; Apoptosis/drug effects/*physiology; Calcium Channel Blockers/pharmacology; Calcium Channels, L-Type/*drug effects/physiology; Cell Death/drug effects/physiology; Cells, Cultured; Cerebellum/*drug effects/physiology; Neurons/*drug effects/physiology; Nicardipine/pharmacology; Peptide Fragments/*pharmacology; Prions/*pharmacology; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't
AD Dipartimento di Oncologia, Universita di Genova, Servizio di Farmacologia e Neuroscienze Istituto Nazionale per la Ricerca sul Cancro (IST), Unita di Neuroscienze, Centro di Biotecnologie Avanzate (CBA), Genoa, I-16132, Italy.
SP englisch
PO USA