Scholarlink

<p>Purpose:Vacuolar protein sorting associated protein 16 (Vps16) is a key component of the Vps core complex (Vps–C) and acts as a tethering protein in membrane fusion. Nevertheless, its role in myocardial ischemia/reperfusion (I/R) remains largely unexplored. Methods:This study established a myocardial I/R model in rats and a hypoxia/reoxygenation (H/R) model using H9c2 cells. Both gain-of-function (via adenovirus-mediated Vps16 overexpression) and loss-of-function (via shRNA-mediated Vps16 knockdown) experiments were conducted. Results:This study showed that Vps16-overexpression improved autophagic flux and cardiac function following I/R in vivo and in vitro. However, the protective effect of Vps16 on cardiomyocytes against I/R injury was nullified when treated with autophagy inhibitors such as Bafilomycin A1 (BafA1). Vps16-knockdown worsened H/R-induced impairment of autophagic flux and cell death in H9c2 cardiomyocytes, while these effects could be reversed by rapamycin (Rapa), an autophagy activator. Mechanistically, Vps16 competed with Rubicon for binding to UVRAG in cardiomyocytes via the residues 333–613, subsequently promoting Rab7 activation, which is essential for the late stage of autophagy. Knockdown of Rubicon successfully mitigated the adverse impact of truncated Vps16 (lacking residues 333–613) in cardiomyocytes. Conclusion:These findings indicate that Vps16 exerts a protective effect against myocardial I/R injury, achieved by promoting autolysosome maturation of and reinstating the autophagic flux in cardiomyocytes.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Vps16 Attenuates Myocardial Ischemia/reperfusion Injury by Interacting with UVRAG and Activating Rab7

  • 期刊论文

  • 发表日期：

    2026年3月19日

查看全文
  • Yuanbin Li,
  • Jinhao Zhou,
  • Dan Wang,
  • Xu Yan,
  • Yiguo Ouyang,
  • Wei Wang,
  • Chenyao Zhu,
  • Zhuang Chen

摘要

Purpose:Vacuolar protein sorting associated protein 16 (Vps16) is a key component of the Vps core complex (Vps–C) and acts as a tethering protein in membrane fusion. Nevertheless, its role in myocardial ischemia/reperfusion (I/R) remains largely unexplored. Methods:This study established a myocardial I/R model in rats and a hypoxia/reoxygenation (H/R) model using H9c2 cells. Both gain-of-function (via adenovirus-mediated Vps16 overexpression) and loss-of-function (via shRNA-mediated Vps16 knockdown) experiments were conducted. Results:This study showed that Vps16-overexpression improved autophagic flux and cardiac function following I/R in vivo and in vitro. However, the protective effect of Vps16 on cardiomyocytes against I/R injury was nullified when treated with autophagy inhibitors such as Bafilomycin A1 (BafA1). Vps16-knockdown worsened H/R-induced impairment of autophagic flux and cell death in H9c2 cardiomyocytes, while these effects could be reversed by rapamycin (Rapa), an autophagy activator. Mechanistically, Vps16 competed with Rubicon for binding to UVRAG in cardiomyocytes via the residues 333–613, subsequently promoting Rab7 activation, which is essential for the late stage of autophagy. Knockdown of Rubicon successfully mitigated the adverse impact of truncated Vps16 (lacking residues 333–613) in cardiomyocytes. Conclusion:These findings indicate that Vps16 exerts a protective effect against myocardial I/R injury, achieved by promoting autolysosome maturation of and reinstating the autophagic flux in cardiomyocytes.