通过与HMGB1相互作用,SNX3调节心力衰竭,随后促进其核-细胞质转移
Hong Li1,2,3, Ming-Xia Peng1, Rui-Xue Yang2,3
1National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangdong Province Engineering Laboratory for Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Acta pharmacologica Sinica
|January 3, 2025
概括
排序nexins (SNXs),特别是SNX3,通过调解高流动性组盒1 (HMGB1) 的核出口来驱动病态心脏缩和心力衰竭. 减少SNX3可以保护心脏免受损伤.
科学领域:
- 心血管生物学 心血管生物学
- 分子细胞生物学 分子细胞生物学
- 贩卖蛋白质 贩卖蛋白质 是一个问题.
背景情况:
- 排序nexins (SNXs) 调节货物蛋白排序,并与各种疾病有关.
- 在蛋白质分类,恢复和降解方面,SNX-逆转激素复合体至关重要.
- 之前的研究表明,SNX3促进心肌细胞中的STAT3激活,这表明心脏的作用.
研究的目的:
- 调查SNX3在病理性心脏缩和心力衰竭的发展中的作用.
- 阐明SNX3有助于心脏功能障碍的分子机制.
主要方法:
- 分别在老鼠和小鼠中建立了腹部大动脉收缩 (AAC) 和横向大动脉收缩 (TAC) 模型.
- 使用异二醇 (ISO) 的新生小鼠心肌细胞 (NRCMs) 中诱导的心脏缩.
- 利用心脏内注射,条件淘汰和淘汰技术来操纵SNX3表达;采用免疫沉质谱和表面等离子体共振来确定蛋白质相互作用.
主要成果:
- 在AAC大鼠的高性NRCM和失败的心脏中,SNX3表达被上调.
- 过度表达SNX3会加剧心力衰竭和ISO诱导的损伤,而SNX3缺乏会提供保护.
- 确定了SNX3-逆转激素和高流动性组盒1 (HMGB1) 之间的直接相互作用,介导HMGB1的核排放.
- HMGB1调节了SNX3的益增高效应和SNX3缺乏的保护作用.
结论:
- 在促进病态心脏缩和心力衰竭方面,SNX3起着至关重要的作用.
- SNX3-逆转子直接与HMGB1相互作用,促进其核出口.
- 针对SNX3-HMGB1相互作用可能为心力衰竭提供治疗策略.
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