Department of Translational Medicine, Federico II University of Naples and URT Genomic of Diabetes of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Via Pansini 5, 80131 Naples, Italy.
Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci. 2023 Jul 25;24(15):11891. doi: 10.3390/ijms241511891.
PREP1 is a homeodomain transcription factor that impairs metabolism and is involved in age-related aortic thickening. In this study, we evaluated the role of PREP1 on endothelial function. Mouse Aortic Endothelial Cells (MAECs) transiently transfected with a cDNA showed a 1.5- and 1.6-fold increase in eNOS and PKCα phosphorylation, respectively. Proinflammatory cytokines and increased by 3.5 and 2.3-fold, respectively, in the presence of , while the antioxidant genes and were significantly reduced. Bisindolylmaleimide reverted the effects induced by PREP1, suggesting PKCα to be a mediator of PREP1 action. Interestingly, resveratrol, a phenolic micronutrient compound, reduced the PREP1 levels, eNOS, PKCα phosphorylation, and proinflammatory cytokines and increased and mRNA levels. The experiments performed on the aorta of 18-month-old hypomorphic heterozygous mice () expressing low levels of this protein showed a 54 and 60% decrease in PKCα and eNOS phosphorylation and a 45% reduction in levels, with no change in , compared to same-age WT mice. However, a significant decrease in and was observed in old mice, indicating the lack of age-induced antioxidant response. These results suggest that deficiency partially improved the endothelial function in aged mice and suggested PREP1 as a novel target of resveratrol.
PREP1 是一种同源结构域转录因子，可损害代谢并参与与年龄相关的主动脉增厚。在这项研究中，我们评估了 PREP1 对内皮功能的作用。瞬时转染 cDNA 的小鼠主动脉内皮细胞 (MAEC) 中，eNOS 和 PKCα 的磷酸化分别增加了 1.5 倍和 1.6 倍。存在 时，促炎细胞因子 和 分别增加了 3.5 倍和 2.3 倍，而抗氧化基因 和 则显著减少。Bisindolylmaleimide 逆转了 PREP1 诱导的作用，表明 PKCα 是 PREP1 作用的介质。有趣的是，白藜芦醇是一种酚类微量营养素化合物，可降低 PREP1 水平、eNOS、PKCα 磷酸化和促炎细胞因子水平，并增加 和 mRNA 水平。在表达这种蛋白质水平较低的 18 个月大的 杂合子 小鼠的主动脉上进行的实验显示，PKCα 和 eNOS 磷酸化减少了 54%和 60%，而 水平减少了 45%，与同年龄的 WT 小鼠相比， 没有变化。然而，在 老年小鼠中观察到 和 显著减少，表明缺乏年龄诱导的抗氧化反应。这些结果表明， 缺乏部分改善了老年小鼠的内皮功能，并表明 PREP1 是白藜芦醇的一个新靶标。
