Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-κB require the cytoplasmic domain of the receptor but different downstream signaling pathways
Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-κB require the cytoplasmic domain of the receptor but different downstream signaling pathways
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DOI：
10.1074/jbc.274.28.19919
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发表时间：
1999-07-09
影响因子：
4.8
通讯作者：
Rauvala, H
中科院分区：
文献类型：
--
作者：
Huttunen, HJ;Fages, C;Rauvala, H
晚期糖基化终产物受体（RAGE）介导两性素包被底物上的神经突生长。RAGE通过其他两种配体（晚期糖基化终产物或淀粉样β肽）连接，被认为在细胞损伤机制中发挥作用，包括细胞氧化应激和转录因子nf - κ B的激活，然而，RAGE在神经突起生长和细胞损伤中的信号通路在很大程度上是未知的。本研究表明，将RAGE转染到神经母细胞瘤细胞可诱导丝状足和神经突在两性激素包被的底物上的延伸。此外，在转染细胞中连接RAGE可增强nf - κ b依赖性转录。RAGE介导的神经突生长和nf - κ B的激活都被RAGE细胞质结构域的缺失所阻断。此外，显性负性Rac和Cdc42抑制了RAGE-两性素相互作用诱导的神经突的延伸，而显性负性Ras抑制了NF-kappa B的激活，而Rac和Cdc42不抑制。这些数据表明，RAGE通过不同的信号通路诱导神经突生长并通过NF-kappa B调节基因表达。
Receptor for advanced glycation end products (RAGE) mediates neurite outgrowth in vitro on amphoterin-coated substrates. Ligation of RAGE by two other ligands, advanced glycation end products or amyloid beta-peptide, is suggested to play a role in cell injury mechanisms involving cellular oxidant stress and activation of the transcription factor NF-kappa B, However, the RAGE signaling pathways in neurite outgrowth and cell injury are largely unknown. Here we show that transfection of RAGE to neuroblastoma cells induces extension of filopodia and neurites on amphoterin-coated substrates. Furthermore, ligation of RAGE in transfected cells enhances NF-kappa B-dependent transcription. Both the RAGE-mediated neurite outgrowth and activation of NF-kappa B are blocked by deletion of the cytoplasmic domain of RAGE. Moreover, dominant negative Rac and Cdc42 but not dominant negative Ras inhibit the extension of neurites induced by RAGE-amphoterin interaction In contrast, the activation of NF-kappa B is inhibited by dominant negative Ras but not Rac or Cdc42, These data suggest that distinct signaling pathways are used by RAGE to induce neurite outgrowth and regulate gene expression through NF-kappa B.