NR AEBN
AU Florio,T.; Grimaldi,M.; Scorziello,A.; Salmona,M.; Bugiani,O.; Tagliavini,F.; Forloni,G.; Schettini,G.
TI Intracellular calcium rise through L-type calcium channels, as molecular mechanism for prion protein fragment 106-126-induced astroglial proliferation
QU Biochemical and Biophysical Research Communications 1996 Nov 12; 228(2): 397-405
PT journal article
AB The infectious prion protein (PrPsc) is the etiologic agent of transmissible neurodegenerative conditions such as scrapie or Creutzfeldt-Jakob disease. Its fragment 106-126 (PrP106-126) has been reported to maintain most of the pathological features of PrPsc. We report here the intracellular mechanisms mediating the proliferative effects of PrP106-126 on rat cortical type I astrocytes. The proliferative effects of PrP106-126 started after 24h of treatment and lasted up to 9 days and was antagonized by the L-type voltage-sensitive calcium channel blocker nicardipine. Microfluorimetric studies showed that PrP106-126 caused a rapid increase in the [Ca+2]i. This effect was prevented by nicardipine, or by Ca(+2)-free conditions, showing that the PrP106-126 enhances [Ca+2]i mobilizing Ca+2 from the extracellular environment. Moreover, binding studies demonstrated a direct interference of PrP106-126 with the dihydropyridine binding site. This is the first evidence that a prion protein fragment directly stimulates the proliferation of astrocytes via an increase in [Ca+2]i through the L-type voltage-sensitive calcium channels.
MH Amino Acid Sequence; Animal; Astrocytes/cytology/*drug effects/physiology; Binding, Competitive; Calcium/*metabolism; Calcium Channel Blockers/pharmacology; Calcium Channels/drug effects/*physiology; Calcium Channels, L-Type; Cell Division/drug effects; Cells, Cultured; Cerebral Cortex/*cytology; DNA/biosynthesis; Isradipine/metabolism; Kinetics; Molecular Sequence Data; Nicardipine/pharmacology; Peptide Fragments/chemical synthesis/*pharmacology; Peptides/chemical synthesis/pharmacology; Prions/chemical synthesis/*pharmacology; Rats; Support, Non-U.S. Gov't; Thymidine/metabolism; Time Factors
AD Istituto di Farmacologia, Facolta di Medicina, Universita di Genova, Italy.
SP englisch
PO USA