9月2日,，The Journal of Biological Chemistry雜志在線發(fā)表了生化與細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,，揭示了胞外信號調(diào)節(jié)激酶ERK通過一個新的下游分子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健康和影響人類生活質(zhì)量的頑癥之一,。與一般的痛覺反應(yīng)不同,，慢性神經(jīng)痛維持時間長，并且對常用的鎮(zhèn)痛劑具有耐受,，是國際上疼痛研究的重點與難題,。在生化細胞所與復(fù)旦大學(xué)長達數(shù)年的合作中,，研究者們發(fā)現(xiàn)了一個在慢性神經(jīng)痛產(chǎn)生和維持過程具有重要功能的基因SIP30,，該部分工作剛剛發(fā)表在國際疼痛學(xué)的專業(yè)雜志Pain上。在JBC的這篇論文中他們發(fā)現(xiàn),，SIP30作為一個突觸小泡運輸相關(guān)蛋白質(zhì),，在動物神經(jīng)痛模型中的表達受重要信號通路ERK的調(diào)控。進一步的機制研究表明,，SIP30作為ERK信號的下游靶基因其表達受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信號的一個新下游分子,，可能參與了慢性神經(jīng)痛的產(chǎn)生和維持過程,。此項研究將有助于加深人們對慢性神經(jīng)痛中樞調(diào)節(jié)機制的認識,，并對慢性神經(jīng)痛治療靶點提供了新的研究方向。
該項研究工作得到了國家科技部,、國家自然基金委,、中國科學(xué)院及上海市科委的經(jīng)費支持。(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.
