Na Hyun-Jin, Kim Jong Min, Kim Yiseul, Lee Sang Hee, Sung Mi-Jeong
Aging and Metabolism Research Group, Food Functionality Research, Korea Food Research Institute, Wanju 55365, Korea.
Prev Nutr Food Sci. 2024 Dec 31;29(4):430-440. doi: 10.3746/pnf.2024.29.4.430.
Vascular smooth muscle cells (VSMCs) undergo metabolic pathway transitions, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, which are important for their function. Metabolic dysfunction in VSMCs can lead to age-related vascular diseases. -GlcNAcylation, a nutrient-dependent posttranslational modification linked specifically to glucose metabolism, plays an important role in this context. DC. (MK), derived from the flower buds of , is known for its anticancer, anti-allergy, and anti-inflammatory properties. However, the role of -GlcNAcylation in VSMCs under aging and the association between MK and -GlcNAc remain unclear. Therefore, the present study aimed to determine the effects of -GlcNAc on VSMC proliferation, along with the expression of MOF (males absent on the first, KAT8) and its correlation with the efficacy of MK. The results showed that aging and -GlcNAc induction increased the expression levels of -GlcNAc, -GlcNAc transferase (OGT), ataxia telangiectasia mutated (ATM) protein, and MOF in mouse vascular smooth muscle cells (MOVAS) and aorta tissue. Transfection with OGT siRNA reduced the expression of MOF and OGT, indicating that OGT regulates MOF and influences cell proliferation. MK treatment reduced the expression of OGT, ATM, and MOF, which was correlated with -GlcNAc levels. These findings suggest that -GlcNAcylation is important for VSMC homeostasis and may be a novel target for vascular diseases. Thus, MK exhibits potential as a new drug candidate for treating vascular diseases by modulating -GlcNAcylation and MOF interactions.
血管平滑肌细胞（VSMCs）会经历代谢途径转变，包括有氧糖酵解、脂肪酸氧化和氨基酸代谢，这些对其功能很重要。VSMCs中的代谢功能障碍会导致与年龄相关的血管疾病。O-连接N-乙酰葡糖胺化（O-GlcNAcylation）是一种与葡萄糖代谢特异性相关的营养依赖性翻译后修饰，在这种情况下起着重要作用。从 花的花蕾中提取的毛喉鞘蕊花提取物（MK）以其抗癌、抗过敏和抗炎特性而闻名。然而，衰老状态下O-GlcNAcylation在VSMCs中的作用以及MK与O-GlcNAc之间的关联仍不清楚。因此，本研究旨在确定O-GlcNAc对VSMC增殖的影响，以及MOF（第一雄性缺失蛋白，KAT8）的表达及其与MK疗效的相关性。结果表明，衰老和O-GlcNAc诱导增加了小鼠血管平滑肌细胞（MOVAS）和主动脉组织中O-GlcNAc、O-GlcNAc转移酶（OGT）、共济失调毛细血管扩张突变蛋白（ATM）和MOF的表达水平。用OGT siRNA转染可降低MOF和OGT的表达，表明OGT调节MOF并影响细胞增殖。MK处理降低了OGT、ATM和MOF的表达，这与O-GlcNAc水平相关。这些发现表明，O-GlcNAcylation对VSMC稳态很重要，可能是血管疾病的一个新靶点。因此，MK通过调节O-GlcNAcylation和MOF相互作用，展现出作为治疗血管疾病新药候选物的潜力。
