Abstract
Prion-related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrP(Sc)) associated with neuronal degeneration and astrogliosis. The synthetic peptide homologous to PrP fragment 106-126 (PrP 106-126) induced in vitro neuronal apoptosis and glial proliferation. We used Northern blot analysis and the RNA polymerase chain reaction to assess the expression of several genes associated with programmed cell death and proliferation. Blots of total RNA extracted from neuronal and astroglial cells exposed to PrP 106-126 for between 1 h and 7 days were hybridized with probes recognizing c-fos, c-jun, c-myc, p53, hsp-70 and bcl-2 mRNA. Except for a slight decrease in bcl-2 mRNA in neuronal cells, no change in other transcripts was evident. Since clusterin (apolipoprotein J) mRNA levels are increased in prion-related encephalopathies and clusterin immunoreactivity has been located in association with PrP(Sc) in Gerstmann-Straussler-Scheinker brain, the expression of clusterin was determined in neuronal and astroglial cells chronically exposed to PrP 106-126, Although the induction of clusterin has been involved in the apoptotic mechanism in other experimental conditions, its expression was unchanged in PrP 106-126-treated neurons, while a three-fold induction of clusterin mRNA was observed in astrocytes exposed to PrP 106-126. To investigate whether the clusterin up-regulation was simply associated with the astroglial proliferative stimulus of PrP 106-126 or was specifically induced by the peptide, we measured clusterin expression in astrocytes cultured in fetal calf serum-free medium and exposed to PrP 106-126 or fetal calf serum restoration. In this condition the PrP peptide, like fetal calf serum, increased the glial proliferation rate, but only PrP 106-126 doubled clusterin mRNA. The selectivity of this effect indicates that PrP(Sc) is directly involved in the clusterin upregulation seen in prion-related encephalopathies and is associated with astroglial cells.
| Original language | English |
|---|---|
| Pages (from-to) | 589-597 |
| Number of pages | 9 |
| Journal | European Journal of Neuroscience |
| Volume | 8 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1996 |
Fingerprint
Keywords
- Apoptosis
- Astrogliosis
- Clusterin
- Gene expression
- Prion-related encephalopathies
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Clusterin (SGP-2) induction in rat astroglial cells exposed to prion protein fragment 106-126. / Chiesa, Roberto; Angeretti, Nadia; Lucca, Elisa; Salmona, Mario; Tagliavini, Fabrizio; Bugiani, Orso; Forloni, Gianluigi.
In: European Journal of Neuroscience, Vol. 8, No. 3, 1996, p. 589-597.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clusterin (SGP-2) induction in rat astroglial cells exposed to prion protein fragment 106-126
AU - Chiesa, Roberto
AU - Angeretti, Nadia
AU - Lucca, Elisa
AU - Salmona, Mario
AU - Tagliavini, Fabrizio
AU - Bugiani, Orso
AU - Forloni, Gianluigi
PY - 1996
Y1 - 1996
N2 - Prion-related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrP(Sc)) associated with neuronal degeneration and astrogliosis. The synthetic peptide homologous to PrP fragment 106-126 (PrP 106-126) induced in vitro neuronal apoptosis and glial proliferation. We used Northern blot analysis and the RNA polymerase chain reaction to assess the expression of several genes associated with programmed cell death and proliferation. Blots of total RNA extracted from neuronal and astroglial cells exposed to PrP 106-126 for between 1 h and 7 days were hybridized with probes recognizing c-fos, c-jun, c-myc, p53, hsp-70 and bcl-2 mRNA. Except for a slight decrease in bcl-2 mRNA in neuronal cells, no change in other transcripts was evident. Since clusterin (apolipoprotein J) mRNA levels are increased in prion-related encephalopathies and clusterin immunoreactivity has been located in association with PrP(Sc) in Gerstmann-Straussler-Scheinker brain, the expression of clusterin was determined in neuronal and astroglial cells chronically exposed to PrP 106-126, Although the induction of clusterin has been involved in the apoptotic mechanism in other experimental conditions, its expression was unchanged in PrP 106-126-treated neurons, while a three-fold induction of clusterin mRNA was observed in astrocytes exposed to PrP 106-126. To investigate whether the clusterin up-regulation was simply associated with the astroglial proliferative stimulus of PrP 106-126 or was specifically induced by the peptide, we measured clusterin expression in astrocytes cultured in fetal calf serum-free medium and exposed to PrP 106-126 or fetal calf serum restoration. In this condition the PrP peptide, like fetal calf serum, increased the glial proliferation rate, but only PrP 106-126 doubled clusterin mRNA. The selectivity of this effect indicates that PrP(Sc) is directly involved in the clusterin upregulation seen in prion-related encephalopathies and is associated with astroglial cells.
AB - Prion-related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrP(Sc)) associated with neuronal degeneration and astrogliosis. The synthetic peptide homologous to PrP fragment 106-126 (PrP 106-126) induced in vitro neuronal apoptosis and glial proliferation. We used Northern blot analysis and the RNA polymerase chain reaction to assess the expression of several genes associated with programmed cell death and proliferation. Blots of total RNA extracted from neuronal and astroglial cells exposed to PrP 106-126 for between 1 h and 7 days were hybridized with probes recognizing c-fos, c-jun, c-myc, p53, hsp-70 and bcl-2 mRNA. Except for a slight decrease in bcl-2 mRNA in neuronal cells, no change in other transcripts was evident. Since clusterin (apolipoprotein J) mRNA levels are increased in prion-related encephalopathies and clusterin immunoreactivity has been located in association with PrP(Sc) in Gerstmann-Straussler-Scheinker brain, the expression of clusterin was determined in neuronal and astroglial cells chronically exposed to PrP 106-126, Although the induction of clusterin has been involved in the apoptotic mechanism in other experimental conditions, its expression was unchanged in PrP 106-126-treated neurons, while a three-fold induction of clusterin mRNA was observed in astrocytes exposed to PrP 106-126. To investigate whether the clusterin up-regulation was simply associated with the astroglial proliferative stimulus of PrP 106-126 or was specifically induced by the peptide, we measured clusterin expression in astrocytes cultured in fetal calf serum-free medium and exposed to PrP 106-126 or fetal calf serum restoration. In this condition the PrP peptide, like fetal calf serum, increased the glial proliferation rate, but only PrP 106-126 doubled clusterin mRNA. The selectivity of this effect indicates that PrP(Sc) is directly involved in the clusterin upregulation seen in prion-related encephalopathies and is associated with astroglial cells.
KW - Apoptosis
KW - Astrogliosis
KW - Clusterin
KW - Gene expression
KW - Prion-related encephalopathies
UR - http://www.scopus.com/inward/record.url?scp=0029966011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029966011&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.1996.tb01244.x
DO - 10.1111/j.1460-9568.1996.tb01244.x
M3 - Article
C2 - 8963451
AN - SCOPUS:0029966011
VL - 8
SP - 589
EP - 597
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 3
ER -