Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Oxid Med Cell Longev. 2020 Oct 2;2020:5950195. doi: 10.1155/2020/5950195. eCollection 2020.
Endothelial injury plays a critical role in the pathogenesis of cardiovascular disorders and metabolic-associated vascular complications which are the leading cause of death worldwide. However, the mechanism underlying endothelial dysfunction is not completely understood. The study is aimed at investigating the role of tubulin polymerization-promoting protein family member 3 (TPPP3) in palmitic acid- (PA-) induced endothelial injury. The effect of TPPP3 on human umbilical vein endothelial cells (HUVECs) was determined by evaluating apoptosis, tube formation, and reactive oxygen species (ROS) production. TPPP3 silencing inhibited PA overload-induced apoptosis and production of ROS, along with the alteration of apoptosis-related key proteins such as BCL-2 and Bax. Mechanically, voltage-dependent anion channel 1 (VDAC1) was identified as a novel functional binding partner of TPPP3, and TPPP3 promoted VDAC1 protein stability and its activity. Further studies indicated that TPPP3 could promote apoptosis, ROS production, tube formation, and proapoptotic protein expression and reduce antiapoptotic protein expression through increasing VDAC1 expression under mildly elevated levels of PA. Collectively, these results demonstrated that TPPP3 could promote PA-induced oxidative damage in HUVECs via a VDAC1-dependent pathway, suggesting that TPPP3 might be considered as a potential therapeutic target in vascular disease.
内皮损伤在心血管疾病和代谢相关血管并发症的发病机制中起着关键作用，这些并发症是全球死亡的主要原因。然而，内皮功能障碍的机制尚不完全清楚。本研究旨在探讨微管蛋白聚合促进蛋白家族成员 3（TPPP3）在棕榈酸（PA）诱导的内皮损伤中的作用。通过评估细胞凋亡、管形成和活性氧（ROS）产生来确定 TPPP3 对人脐静脉内皮细胞（HUVEC）的影响。TPPP3 沉默抑制了 PA 过载诱导的细胞凋亡和 ROS 产生，以及凋亡相关关键蛋白如 BCL-2 和 Bax 的改变。在机制上，电压依赖性阴离子通道 1（VDAC1）被鉴定为 TPPP3 的一个新的功能结合伙伴，TPPP3 促进了 VDAC1 蛋白的稳定性及其活性。进一步的研究表明，TPPP3 可以通过增加轻度升高的 PA 下的 VDAC1 表达，促进细胞凋亡、ROS 产生、管形成和促凋亡蛋白的表达，降低抗凋亡蛋白的表达。总之，这些结果表明，TPPP3 可以通过 VDAC1 依赖性途径促进 PA 诱导的 HUVEC 氧化损伤，提示 TPPP3 可能被视为血管疾病的潜在治疗靶点。
