Advanced-glycation-end-product-induced formation of immunoproteasomes: involvement of RAGE and Jak2/STAT1.
Biochem J
; 448(1): 127-39, 2012 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-22892029
ABSTRACT
AGEs (advanced glycation-end products) accumulate during aging and several pathologies such as Alzheimer's disease and diabetes. These protein products are known to inhibit proteolytic pathways. Moreover, AGEs are known to be involved in the activation of immune responses. In the present study we demonstrate that AGEs induce the expression of immunoproteasomal subunits. To elucidate a molecular basis underlying the observed effects we were able to demonstrate an activation of the Jak2 (Janus kinase 2)/STAT1 (signal transducer and activator of transcription 1) pathway. Inhibition of Jak2 by AG-490 and STAT1 by specific siRNA (small interfering RNA) abolished AGE-induced expression of immunoproteasomal subunits. Furthermore, silencing of RAGE (receptor for AGEs) revealed that AGE-induced up-regulation of the immunoproteasome is mediated by a RAGE signalling process. Thus we have described for the first time that the signalling pathway of Jak2 and STAT1 activated by AGEs via RAGE is involved in the induction of the immunoproteasome.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores Imunológicos
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Transdução de Sinais
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Produtos Finais de Glicação Avançada
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Complexo de Endopeptidases do Proteassoma
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Fator de Transcrição STAT1
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Janus Quinase 2
Limite:
Animals
Idioma:
En
Revista:
Biochem J
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha