Prion protein (PrP) inhibits the activation of proapoptotic Bax in primary human neurons and MCF-7 cells. Because neuronal apoptosis occurs in human prion diseases, here we examine the anti-Bax function of familial PrP mutants. All Creutzfeldt-Jakob disease and fatal familial insomnia-associated prion protein mutations partially or completely lose the anti-Bax function in human neurons and, except for A117V and V203I, in MCF-7 cells. The ability of the mutants to protect against Bax-mediated cell death is divided into three groups: (1) group I, retention of anti-Bax function in both the Val129 and Met129 mutants; (2) group II, retention of anti-Bax function only in Val129 mutants; and (3) group III, reduction or no anti-Bax function in Val129 and Met129 mutants. The loss of anti-Bax function in these PrP mutants correlates completely with a significant decrease in the production of cytosolic PrP, a form of PrP shown previously to have anti-Bax function in human neurons. Cotransfection of the full-length PrP mutants with wild-type or mutant cytosolic PrP, but not with wild type full-length PrP, rescues the anti-Bax function of PrP. The results show that the failure of PrP mutants to produce cytosolic PrP is responsible for the loss of anti-Bax function and that the effect of the PrP mutants is dominant over wild-type PrP. Furthermore, these results imply that misfolded PrP that escapes retrotranslocation could accumulate at the cell surface and cause neuronal dysfunction.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672383 | PMC |
http://dx.doi.org/10.1523/JNEUROSCI.0957-07.2007 | DOI Listing |
J Mol Histol
August 2024
Department of Anatomy, College of Medicine and Medical Sciences, Arabian Gulf University, P.O Box: 26671, Manama, Bahrain.
Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects.
View Article and Find Full Text PDFJ Comp Pathol
October 2023
Department of Virology, Faculty of Veterinary Medicine, University of Ankara, Diskapi, 06110 Ankara, Turkiye.
Acute demyelinating leucoencephalomyelitis was the most conspicuous microscopic change in the brain and spinal cord of kids infected with caprine arthritis encephalitis virus (CAEV). TUNEL positivity and labelling of anti-bax and anti-caspases-3, -8 and -9 were found in a distinct population of glial cells, mainly at the edges of the demyelinated plaques and perivascular areas and, to a lesser extent, in neurons. Double labelling revealed that most of these apoptotic cells in the demyelinated plaques were astrocytes and a few were oligodendroglia.
View Article and Find Full Text PDFBioengineered
March 2022
Department of Clinical Laboratory, Suizhou Hospital, Hubei University of Medicine, Suizhou, China.
Circular RNA circ_0000285 is differentially expressed in several malignancies; however, its role in gliomas is under investigation. Reverse transcription quantitative polymerase chain reaction was conducted to evaluate the expression of circ_0000285, miR-197-3p, and CDC28 protein kinase regulatory subunit 1B (CKS1B) in glioma tissues and cells. Cell Counting Kit-8 and Transwell invasion assays coupled with Western blotting analysis using anti-Bax and anti-Bcl-2 antibodies were performed to evaluate cell proliferation, invasion, and apoptosis.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2021
Department of Dermatology, Hubei Provincial Hospital of TCM, Wuhan, 430000, Hubei, China. Electronic address:
Long non-coding RNA (lncRNA) homeobox (HOX) A11 antisense (HOXA11-AS) mediates cell-biological phenotypes of keloid fibroblasts and influence the keloid progression, yet the underlying mechanism need to be further understood. HOXA11-AS, microRNA miR-148b-3p and Insulin like growth factor binding protein 5 (IGFBP5) expression were detected by RT-qPCR or western blot. CCK-8 and colony formation assays were applied to examine the cell proliferation.
View Article and Find Full Text PDFDiagn Pathol
February 2019
Department of Oral Pathology, São Leopoldo Mandic Research Institute, Rua José Rocha Junqueira, 13, CEP, Campinas, SP, 13045-610, Brazil.
Background: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with poor long-term survival, which warrants studies aimed at clarifying the pathogenesis of this disease in order to widen the scope of therapeutic options currently available. Alterations in regulatory mechanisms relating to vascular support, cell death and autophagy are important pathways for tumor growth in cancer. Thus, the present study aimed to access vascular supply, apoptosis, autophagy and cell senescence in ACC of minor salivary glands.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!