The infectious prion protein (PrP(Sc)) 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 PrP(Sc). 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 24 h of treatment and lasted up to 9 days and was antagonized by the L-type voltage-sensitive calcium channel blocker nicardipine. Microfluorimetric studies shelved that PrP106-126 caused a rapid increase in the [Ca++](i). This effect was prevented by nicardipine, or by Ca++-free conditions, showing that the PrP106-126 enhances [Ca++](i) mobilizing Ca++ 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++](i) through the L-type voltage-sensitive calcium channels.
|Number of pages||9|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - Nov 12 1996|
ASJC Scopus subject areas
- Molecular Biology