The Prion Protein and Its Paralogue Doppel Affect Calcium Signaling in Chinese Hamster Ovary Cells

Alterations in Ca2+-Buffering in Prion-Null Mice: Association with Reduced Afterhyperpolarizations in CA1 Hippocampal Neurons

“…2؉ signaling Several studies have implicated changes in Ca 2ϩ homeostasis in the absence of PrP (Herms et al, 2000(Herms et al, , 2001Brini et al, 2005;Fuhrmann et al, 2006). The flash photolysis study (Fig.…”

“…Endogenous Ca 2؉ buffering capacity We used the "added buffer" technique (Neher, 1995) to investigate whether the PrP-dependent differences in Ca 2ϩ signaling, found in this and other studies (Herms et al, 2000;Brini et al, 2005;Fuhrmann et al, 2006), could be explained by changes in endogenous Ca 2ϩ binding capacity. Diffusion of Fura-2 from the patch pipette provided controlled loading of Ca 2ϩ buffer into the neurons, with simultaneous recording of calcium responses triggered by somatic depolarization (50 ms duration Ϫ65 to ϩ5 mV, every 30 s).…”

“…In cerebellar granule neurons, basal levels and depolarization-induced Ca 2ϩ signals are reduced without observed alterations in VGCC function (Herms et al, 2000). Prion protein expression has also been shown to have profound effects on Ca 2ϩ signaling in Chinese hamster ovary cells (Brini et al, 2005).…”

Physiological role of prions in regulation of Ca2+-transport and neurodegenerative diseases

“…Використання Ca 2+ -чутливих зондів "Aequorins" допомогло дослідити роль амі-лоїдних протеїнів (агрегатів PrP Sc ) у порушенні гомеостазу Ca 2+ в цитоплазмі, про-світі ЕПС і матриксі мітохондрій [16]. Зокрема, під час зараження культури клітин нейронів очищеним PrP Sc відбувається значне збільшення рівня цитозольного Ca…”

Doppel induces autophagic stress in prion protein-deficient Purkinje cells

“…Cytosolic Dpl itself can induce ROS production (4) through a calcium-dependent mechanism. 20 ROS is a known inducer of autophagy (5), 10 as well as apoptosis through JNK (6) activation of Bax-dependent (7) and caspase-8-dependent (8) apoptotic pathways. Independently of its role in cell survival (9), autophagy is able to either cause autophagic cell death (10) or induce Bax-dependent apoptosis (11).…”