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Human prion protein mutants with deleted and inserted octarepeats undergo different pathways to trigger cell apoptosis.
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- Author(s): Xu K;Xu K; Wang X; Shi Q; Chen C; Tian C; Li XL; Zhou RM; Chu YL; Dong XP
- Source:
Journal of molecular neuroscience : MN [J Mol Neurosci] 2011 Mar; Vol. 43 (3), pp. 225-34. Date of Electronic Publication: 2010 Jun 05.- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: Humana Press Country of Publication: United States NLM ID: 9002991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1166 (Electronic) Linking ISSN: 08958696 NLM ISO Abbreviation: J Mol Neurosci Subsets: MEDLINE
- Publication Information: Publication: Totowa, NJ : Humana Press
Original Publication: Boston : Birkhäuser [i.e. Cambridge, MA : Birkhäuser Boston, c1989- - Subject Terms: Repetitive Sequences, Amino Acid*; Apoptosis/*physiology ; Mutant Proteins/*genetics ; Prions/*genetics; Cell Line, Tumor ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Chaperone BiP ; Heat-Shock Proteins/metabolism ; Humans ; Mitochondria/metabolism ; Mutant Proteins/metabolism ; PrPSc Proteins/genetics ; PrPSc Proteins/metabolism ; Prions/metabolism ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism
- Abstract: Octarepeats region sequence is one of the most important characteristics of PrP topology. To explore the mechanism of deleted and inserted octarepeats mutants PrP-caused apoptosis, wild-type PrP (PrP-PG5), and PrP with deleted octarepeats (PrP-PG0) and with four (PrP-PG9) and seven (PrP-PG12) extra octarepeats were transiently induced into SH-SY5Y cell. The results indicated PrP-PG9 and PrP-PG12 mainly retained in fraction of cytoplasm, while PrP-PG5 and PrP-PG0 presented both in cell membrane and cytoplasm. Cells expressing PrP-PG9 and PrP-PG12 were sensitive to endoplasmic reticulum (ER) stimuli, tunicamycin, and brefeldin A. ER-stress-related proteins, Grp94, XBP1, TRAF2, and CHOP, were significantly increased in cells expressing PrP-PG9 and PrP-PG12, while Grp78 increased markedly 12 h and pro-caspase-12 decreased sharply 20 h post-transfection. It indicates that expressions of PrP mutants with inserted octarepeats cause ER stress and lead to cell apoptosis lately. Meanwhile, cellular Cytochrome C increased and Bcl-2 decreased obviously in cells expressing PrP-PG0, indicating triggering a mitochondrial-related apoptosis. These data highlight that PrP mutants in region of octarepeats may undergo different pathways to trigger cell apoptosis, in which PrPs with inserted octarepeats via ER stress and PrP mutant without octarepeats via mitochondrial-related pathway.
- Accession Number: 0 (Endoplasmic Reticulum Chaperone BiP)
0 (HSPA5 protein, human)
0 (Heat-Shock Proteins)
0 (Mutant Proteins)
0 (PrPSc Proteins)
0 (Prions)
0 (Recombinant Proteins) - Publication Date: Date Created: 20100608 Date Completed: 20110721 Latest Revision: 20211203
- Publication Date: 20231215
- Accession Number: 10.1007/s12031-010-9387-0
- Accession Number: 20526696
- Source:
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