Identification of novel putative-binding proteins for cellular prion protein and a specific interaction with the STIP1 homology and U-Box-containing protein 1.

Prion diseases involve the conversion of the endogenous cellular prion protein, PrP(C), into a misfolded infectious isoform, PrP(Sc). Several functions have been attributed to PrP(C), and its role has also been investigated in the olfactory system. PrP(C) is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp(-/-) mice showed impaired behavior in olfactory tests. Given the high PrP(C) expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrP(C)-binding partners. Ten different putative PrP(C) ligands were identified, which were involved in functions such as cellular proliferation and apoptosis, cytoskeleton and vesicle transport, ubiquitination of proteins, stress response, and other physiological processes. In vitro binding assays confirmed the interaction of PrP(C) with STIP1 homology and U-Box containing protein 1 (Stub1) and are reported here for the first time. Stub1 is a co-chaperone with ubiquitin E3-ligase activity, which is associated with neurodegenerative diseases characterized by protein misfolding and aggregation. Physiological and pathological implications of PrP(C)-Stub1 interaction are under investigation. The PrP(C)-binding proteins identified here are not exclusive to the OE, suggesting that these interactions may occur in other tissues and play general biological roles. These data corroborate the proposal that PrP(C) is part of a multiprotein complex that modulates several cellular functions and provide a platform for further studies on the physiological and pathological roles of prion protein.

Flow cytometric immune profiling of specific-pathogen-free chickens before and after infectious challenges.

Broilers and layer chickens have been intensively selected for production parameters. This selection has affected immune capacity. Consequently, the fine-tuning of immune responses is becoming important for maximum productivity. Flow cytometry is a recurrent technology used for the immunophenotyping of birds. Studies, however, have focused on the mechanism of specific diseases or have used animals whose immunological condition could be biased-by vaccination or environmental stressors, for example. The aim of this study was to evaluate the immune status of specific-pathogen-free birds across different age ranges to characterize the natural changes that occur over time. Additionally, specific-pathogen-free chickens were challenged with four infectious agents, allowing identification of the subpopulations of peripheral blood immune cells that are consistently altered under various conditions. Several lymphocyte subsets vary naturally with aging, so the interpretation of results using animals of different age ranges must proceed with care. Parameters such as CD8(+)CD28(-), CD8αα(+), CD4(+)CD8(+), and CD8(+)TCRVß1(+) have been shown to be valuable in understanding immune changes during disease. The use of these data allows a determination of the consistency of cytometric parameters under various conditions, which should ease the interpretation of immunophenotyping and the future application of cytometric analysis in the poultry industry.

O envelhecimento sob o ponto de vista molecular e celular / Molecular and cellular aspects of aging

Este artigo tem como objetivo introduzir as teorias evolutivas do envelhecimento e as suas discussões, e também apresentar as recentes pesquisas sobre as bases moleculares e celulares do envelhecimento.

O envelhecimento sob o ponto de vista molecular e celular / Molecular and cellular aspects of aging

Este artigo tem como objetivo introduzir as teorias evolutivas do envelhecimento e as suas discussões, e também apresentar as recentes pesquisas sobre as bases moleculares e celulares do envelhecimento

Caracterização e implicações fisiológicas das interações da proteína prion celular com o seu receptor de 60-66 kDa e com a laminina / Caracterization and physiological implications of the cellular prion protein interactions with its 60-66 kDa receptor and with laminin

Prions são definidos como partículas protéicas infecciosas compostas, quase que exclusivamente, por uma proteína conhecida como prion scrapie (PrPsc). O envolvimento dessas partículas na etiologia de doenças neurodegenerativas, tanto em homens como em animais, já está bem determinado. Acredita-se que o PrPsc seja sintetizado através de modificações pós-traducionais que ocorreriam na isoforma celular da proteína prion (PrPc), uma glicoproteína expressa constitutivamente na superfície de vários tipos celulares, principalmente de neurônios, ancorada na membrana plasmática por glicosil-fosfatidil inositol (GPI). Apesar de ser uma molécula conservada em várias espécies, a função de PrPc ainda permanece desconhecida. Interessados nos possíveis papéis fisiológicos desempenhados pelo PrPc, decidimos investigar certas interações que o PrPc poderia realizar com outras moléculas, na tentativa de se encontrar pistas sobre a função dessa proteína em células normais...