Raf1 interacts with OIP5 to participate in oxaliplatin-induced neuropathic pain
Raf1 interacts with OIP5 to participate in oxaliplatin-induced neuropathic pain
复制标题
Raf1与OIP5相互作用参与奥沙利铂诱导的神经性疼痛
DOI：
10.1016/j.lfs.2021.119804
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发表时间：
2021-07-05
期刊：
影响因子：
6.1
通讯作者：
Shao，Jinping
中科院分区：
文献类型：
--
作者：
Yu，Wenli;Zheng，Zhenli;Shao，Jinping
奥沙利铂是一种有效的抗癌铂类化疗药物，但其可引起严重的慢性神经病变，其分子机制尚不清楚。Opa相互作用蛋白5（OIP 5）是癌症/睾丸抗原（CTA）家族的成员，并且参与多种癌症。研究表明，Raf 1是一种丝氨酸/苏氨酸蛋白激酶，可直接与OIP 5联合收割机结合，促进其表达。Raf 1和OIP 5是否参与奥沙利铂诱导的神经病理性疼痛尚未见报道。主要方法本研究采用腹腔注射奥沙利铂制备奥沙利铂诱导的神经病理性疼痛模型。通过鞘内注射针对Raf 1和OIP 5的siRNA（siRaf 1、siOIP 5）来敲除OIP 5和Raf 1。采用VonFrey纤维和丙酮检测大鼠痛行为，Western blot检测大鼠背根神经节（DRG）中OIP 5和Raf 1蛋白表达的变化。鞘内注射siOIP 5抑制OIP 5的表达不仅能有效减轻奥沙利铂诱导的机械性痛觉超敏和冷痛敏，而且能降低Raf 1的蛋白表达。鞘内注射siRaf 1可抑制OIP 5的表达，减轻奥沙利铂诱导的神经病理性疼痛。Significance本研究证实Raf 1与OIP 5相互作用参与奥沙利铂诱导的神经病理性疼痛。OIP 5在正常组织中的有限表达可能使其成为治疗奥沙利铂诱导的神经病理性疼痛的理想药物靶点。
AimsOxaliplatin is an effective anti-cancer platinum-based chemotherapy drug which can cause severe chronic neuropathy, but the molecular mechanism underlying this adverse effect is still unclear. Opa interacting protein 5 (OIP5) is a member of the cancer/testis antigen (CTA) family and is involved in a variety of cancers. Studies have shown that Raf1, which is a serine/threonine-protein kinase, can directly combine with OIP5 to promote its expression. Whether Raf1 and OIP5 can participate in oxaliplatin-induced neuropathic pain has not been reported.Main methodsIn this study, the oxaliplatin-induced neuropathic pain model was prepared by intraperitoneal injection of oxaliplatin. OIP5 and Raf1 were knocked down by intrathecal injection of siRNA against Raf1 and OIP5 (siRaf1, siOIP5). Von Frey fiber and acetone were used to detect pain behavior, and western blot was used to detect the protein expression changes of OIP5 and Raf1 in the dorsal root ganglion (DRG).Key findingsThe expression levels of p-Raf1 and OIP5 were increased in DRGs of oxaliplatin-induced neuropathic pain rats. Intrathecal administration of siOIP5 to inhibit the expression of OIP5 not only effectively alleviated oxaliplatin-induced mechanical allodynia and cold hyperalgesia, but also decreased the protein expression of Raf1. Intrathecal administration of siRaf1 inhibited the expression of OIP5 and attenuated oxaliplatin-induced neuropathic pain.SignificanceThis study confirmed that Raf1 interacts with OIP5 to participate in oxaliplatin-induced neuropathic pain. The restricted expression of OIP5 in normal tissues may make it an ideal drug target for the treatment of oxaliplatin-induced neuropathic pain.