Advanced-glycation-end-product-induced formation of immunoproteasomes: involvement of RAGE and Jak2/STAT1

被引：75

作者：

Grimm, Stefanie ^{[1
,2
]}

Ott, Christiane ^{[1
]}

Hoerlacher, Melanie ^{[2
]}

Weber, Daniela ^{[1
,2
]}

Hoehn, Annika ^{[1
,2
]}

Grune, Tilman ^{[1
]}

机构：

[1] Univ Jena, Inst Nutr, D-07743 Jena, Germany

[2] Univ Hohenheim, Inst Biol Chem & Nutr, D-70593 Stuttgart, Germany

来源：

BIOCHEMICAL JOURNAL | 2012年 / 448卷

关键词：

advanced glycation end-product; immunoproteasome; Janus kinase 2 (Jak2); receptor for advanced glycation end-products (RAGE); signal transducer and activator of transcription 1 (STAT1); INTERFERON-GAMMA; RECEPTOR RAGE; ANTIGEN PRESENTATION; ALZHEIMERS-DISEASE; INDUCED ACTIVATION; NEURITE OUTGROWTH; PROTEASOME; CELLS; AGE; AMPHOTERIN;

D O I：

10.1042/BJ20120298

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：127 / 139

页数：13

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