9月2日,，The Journal of Biological Chemistry雜志在線發(fā)表了生化與細(xì)胞所景乃禾研究組與復(fù)旦大學(xué)神經(jīng)生物學(xué)研究所張玉秋研究組合作的最新研究成果，揭示了胞外信號(hào)調(diào)節(jié)激酶ERK通過(guò)一個(gè)新的下游分子SIP30,，參與調(diào)節(jié)慢性神經(jīng)痛,。
慢性神經(jīng)痛是一種廣泛困擾人類(lèi)健康和影響人類(lèi)生活質(zhì)量的頑癥之一,。與一般的痛覺(jué)反應(yīng)不同，慢性神經(jīng)痛維持時(shí)間長(zhǎng),，并且對(duì)常用的鎮(zhèn)痛劑具有耐受,，是國(guó)際上疼痛研究的重點(diǎn)與難題,。在生化細(xì)胞所與復(fù)旦大學(xué)長(zhǎng)達(dá)數(shù)年的合作中,，研究者們發(fā)現(xiàn)了一個(gè)在慢性神經(jīng)痛產(chǎn)生和維持過(guò)程具有重要功能的基因SIP30，該部分工作剛剛發(fā)表在國(guó)際疼痛學(xué)的專業(yè)雜志Pain上,。在JBC的這篇論文中他們發(fā)現(xiàn),，SIP30作為一個(gè)突觸小泡運(yùn)輸相關(guān)蛋白質(zhì)，在動(dòng)物神經(jīng)痛模型中的表達(dá)受重要信號(hào)通路ERK的調(diào)控,。進(jìn)一步的機(jī)制研究表明,，SIP30作為ERK信號(hào)的下游靶基因其表達(dá)受ERK下游轉(zhuǎn)錄因子CREB的調(diào)節(jié),。這些結(jié)果提示，SIP30作為ERK信號(hào)的一個(gè)新下游分子,，可能參與了慢性神經(jīng)痛的產(chǎn)生和維持過(guò)程,。此項(xiàng)研究將有助于加深人們對(duì)慢性神經(jīng)痛中樞調(diào)節(jié)機(jī)制的認(rèn)識(shí)，并對(duì)慢性神經(jīng)痛治療靶點(diǎn)提供了新的研究方向,。
該項(xiàng)研究工作得到了國(guó)家科技部,、國(guó)家自然基金委、中國(guó)科學(xué)院及上海市科委的經(jīng)費(fèi)支持,。(生物谷Bioon.com)
生物谷推薦原始出處：
J. Biol. Chem., Sep 2009; doi:10.1074/jbc.M109.036756
SIP30 is regulated by ERK in peripheral nerve injury-induced neuropathic pain
Guangdun Peng1, Mei Han2, Yimin Du3, Anning Lin4, Lei Yu5, Yuqiu Zhang2, and Naihe Jing1*
From the 1 Institute of Biochemistry and Cell Biology, China; , 2 Institute of Neurobiology, Fudan University, China; , 3 School of Life Sciences, Fudan University, China; , 4 Ben May Department for Cancer Research, The University of Chicago, United States; , 5 Rutgers University, United States
Extracellular signal-regulated kinase (ERK) plays an important role in chronic neuropathic pain. However, the underlying mechanism is largely unknown. Here we show that in chronic constriction injury (CCI) treated rat spinal cords, upregulation of SNAP25 interacting protein 30 (SIP30), which is involved in the development and maintenance of CCI-induced neuropathic pain, correlates with ERK activation and that the upregulation of SIP30 is suppressed by intrathecal delivery of the MEK inhibitor U0126. In PC12 cells, upregulation of SIP30 by nerve growth factor (NGF) is also dependent on ERK activation. We found that there is an ERK-responsive region in the rat SIP30 promoter. Activation of ERK promotes the recruitment of the transcription factor cyclic AMP response element binding protein (CREB) to the SIP30 gene promoter. Taken together, our results provide a potential downstream target of ERK activation mediated neuropathic pain.
