9月2日，The Journal of Biological Chemistry杂志在线发表了生化与细胞所景乃禾研究组与复旦大学神经生物学研究所张玉秋研究组合作的最新研究成果，揭示了胞外信号调节激酶ERK通过一个新的下游分子SIP30，参与调节慢性神经痛。
慢性神经痛是一种广泛困扰人类健康和影响人类生活质量的顽症之一。与一般的痛觉反应不同，慢性神经痛维持时间长，并且对常用的镇痛剂具有耐受，是国际上疼痛研究的重点与难题。在生化细胞所与复旦大学长达数年的合作中，研究者们发现了一个在慢性神经痛产生和维持过程具有重要功能的基因SIP30，该部分工作刚刚发表在国际疼痛学的专业杂志Pain上。在JBC的这篇论文中他们发现，SIP30作为一个突触小泡运输相关蛋白质，在动物神经痛模型中的表达受重要信号通路ERK的调控。进一步的机制研究表明，SIP30作为ERK信号的下游靶基因其表达受ERK下游转录因子CREB的调节。这些结果提示，SIP30作为ERK信号的一个新下游分子，可能参与了慢性神经痛的产生和维持过程。此项研究将有助于加深人们对慢性神经痛中枢调节机制的认识，并对慢性神经痛治疗靶点提供了新的研究方向。
该项研究工作得到了国家科技部、国家自然基金委、中国科学院及上海市科委的经费支持。(生物谷Bioon.com)
生物谷推荐原始出处：
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.
