Royal jelly-induced neurite outgrowth from rat pheochromocytoma PC12 cells requires integrin signal independent of activation of extracellular signal-regulated kinases
Royal jelly-induced neurite outgrowth from rat pheochromocytoma PC12 cells requires integrin signal independent of activation of extracellular signal-regulated kinases
复制标题
DOI：
10.2220/biomedres.28.139
复制
发表时间：
2007-06-01
影响因子：
1.2
通讯作者：
Furukawa, Shoei
中科院分区：
文献类型：
--
作者：
Hattori, Noriko;Nomoto, Hiroshi;Furukawa, Shoei
我们早先发现大鼠嗜铬细胞瘤PC 12细胞的神经突生长被皇家浆提取物（PERJ）或其独特成分AMP N-1-氧化物通过腺苷A2 a受体刺激。在这项研究中，我们发现刺激神经突起生长发生在培养基中补充血清，但不是在无血清培养基。五肽GRGDS，其中包括细胞外基质（ECM）组分共享的RGD序列，可以减弱血清的作用，表明整合素受体信号传导是必不可少的PERJ或AMP N-1-氧化物诱导的神经突生长。PERJ或AMP N-1-氧化物也激活细胞外信号调节激酶1或2（ERK 1/2）;然而，这种激活与神经突生长无关。Mn ~（2+）诱导PC 1/2细胞突起生长，并通过整合素信号激活ERK_（1/2），而ERK_（1/2）的激活是Mn ~（2+）诱导的突起生长所必需的，提示Mn ~（2+）诱导的突起生长与PERJ-或AMP N-1-氧化物诱导的突起生长的机制不同。此外，我们证明PERJ不含ECM成分样物质。这些结果表明，AMP N-1-氧化物及其类似物是PERJ中唯一具有神经突生长诱导活性的实体，并且除了激活A2 a受体外，它们还需要整合素信号传导来诱导神经突生长。
We showed earlier that neurite outgrowth of rat pheochromocytoma PC12 cells was stimulated by royal jelly extract (PERJ) or its unique component, AMP N-1-oxide, via adenosine A2a receptors. In this study, we found that stimulated neurite outgrowth occurred in medium supplemented with serum, but not in serum-free medium. The pentapeptide GRGDS, which includes the RGD sequence commonly shared by extracellular matrix (ECM) components, could attenuate the effect of serum, suggesting that integrin receptor signaling was essential for the neurite outgrowth induced by PERJ or AMP N-1-oxide. PERJ or AMP N-1-oxide also activated extracellular signal-regulated kinases 1 or 2 (ERK1/2); however, this activation was not associated with the neurite Outgrowth. As it is known that Mn2+ induces neurite Outgrowth from PC12 cells and activates ERK1/2 through integrin signals and that activation of ERK1/2 is essential for Mn2+-induced neurite out- growth, a difference in the mechanism between Mn2+-induced and PERJ- or AMP N-1-oxide-mduced neurite outgrowth is suggested. Furthermore, we demonstrated that PERJ contained no ECM component-like substances. These results demonstrate that AMP N-1-oxide and its analogues were the only entities in PERJ with neurite outgrowth-inducing activity and that they required integrin signaling in addition to activation of A2a receptors to induce neurite outgrowth.