干预死亡相关蛋白激酶1–p53相互作用对中风发挥治疗作用-武汉天德生物科技有限公司

Stroke. 2014年10月;45(10):3089-91. doi: 10.1161/STROKEAHA.114.006348. 电子出版日期：2014年8月19日。

Intervention of Death-Associated Protein Kinase 1–p53 Interaction Exerts the Therapeutic Effects Against Stroke

期刊: Stroke	发表时间: 2014-08-19	影响因子:
作者列表: Xiaoxi Wang, MD, Lei Pei, PhD, Honglin Yan, MD, Zhongping Wang, PhD, Na Wei, MD, Shan Wang, MD, Xin Yang, MD, Qing Tian, MD, and Youming Lu, PhD
第一作者国家: 中国	第一作者单位: 华中科技大学、九江学院
通讯作者国家: 中国	通讯作者单位: 华中科技大学、九江学院

研究领域：生物学医学药理学

关键字：重组融合蛋白、卒中、死亡相关蛋白激酶、疾病模型，动物、小鼠、神经保护剂、动物、蛋白质相互作用结构域与基序、tat 基因产物、人类免疫缺陷病毒、肿瘤抑制蛋白 p53、肽类

摘要

Background and Purpose— Death-associated protein kinase 1 (DAPK1) interacts with the tumor suppressor gene p53 via a direct binding of a death domain of DAPK1 to a DNA-binding motif (DM) of p53 (p53DM) and converges multiple cell death pathways in stroke. The goals of this study are to determine whether disruption of DAPK1–p53 interaction is therapeutically effective against stroke.

Methods— We synthesized a membrane-permeable p53DM peptide (Tat-p53DM) and tested the therapeutic effects of Tat-p53DM in a mouse model with stroke.

Results— We showed that Tat-p53DM blocked DAPK1–p53 interaction in brain cells in vivo. When administered 6 hours after stroke onset in adult male mice, Tat-p53DM was still therapeutically effective against brain damages and improved neurological functions.

Conclusions— DAPK1–p53 interaction is a preferred target for therapeutic intervention of stroke.

该研究中，武汉百意欣生物科技有限公司（现武汉天德生物科技有限公司）协助提供多肽合成服务。“由武汉百意欣生物科技有限公司合成了纯度为 99% 的 Tat-p53DM（Tat-RVCACPGRDRRT）肽和 Tat-s-p53DM（Tat-CCPGECVRTRRR）肽。这些肽段进行了统一编号，所有实验均采用盲法操作。”(Tat-p53DM (Tat-RVCACPGRDRRT) or Tat-s-p53DM (Tat-CCPGECVRTRRR) peptides with 99% purity were synthesized by Bioyeargene Biosciences (Wuhan, China). The peptides were numbered, and the experimenters were unaware of which one was applied in all experiments.)