NR AWJT
AU Massimino,M.L.; Stella,R.; Ferrari,J.; Bertoli,A.; Sorgato,M.C.
TI Pursuing the biological function of PrPc by means of a novel experimental paradigm
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-29
PT Konferenz-Poster
AB
The prion protein (PrP) is a highly dynamic mammalian glycoprotein that presents in at least two different conformational isoforms. While it is accepted that the "scrapie" isoform (PrPsc) is the etiologic agent of prion disease, the physiologic role of the normal "cellular" conformer (PrPc) is still elusive, despite the numerous functions proposed by in vitro and in vivo studies, including a role in signal transduction, cell adhesion and survival. Recently, however, accumulating data supports the notion that PrPc serves in neurogenesis and in the differentiation process of neurons. Although these cells represent the model of election where to study PrPc biology, the protein is nonetheless expressed at appreciable levels in other tissues, i.e. skeletal muscles. In this regard, using primary mouse myocytes, we have recently shown that the expression and metabolism of PrPc change during in vitro myogenesis and in skeletal muscle fibres with different contractile properties (Massimino et al. 2006). This suggests that the protein may play an active role in skeletal muscle differentiation and in the maintenance of muscle functions. To explore this issue further, we have applied an in vivo degeneration/regeneration paradigm to wild-type (WT) and PrP-knockout (KO) mice, consisting in treating hind-limb Tibialis anterior with cardiotoxin, a myotoxin that provokes the specific degeneration of muscle fibres, while leaving intact nerves, blood supply and muscle precursor cells. The with-time muscle regeneration was followed by comparing several histologic and biochemical parameters of the two animal types, among which the maturation and dimension of fibres, and the expression of myogenic factors and muscle maturation markers. Taken together, our results show that a different kinetics of regeneration pertains to the two mouse lines. Being the process delayed in KO with C respect to WT mice, these observations suggest that PrP may indeed act as a differentiative molecule in skeletal muscles.
(Massimino M.L. et al. (2006) Heterogeneous PrP metabolism in skeletal muscle cells. FEBS Lett. 580, 878-884.)
AD Department of Biological Chemistry, University of Padova, Padova, Italy
SP englisch
PO Italien