Department of Physical Therapy, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, 701.
Mol Nutr Food Res. 2019 May;63(10):e1801353. doi: 10.1002/mnfr.201801353. Epub 2019 Apr 10.
Atherosclerotic cardiovascular disease is the most prevalent cause of mortality and morbidity. Fucoxanthin (FX) possesses anti-hypertensive and anti-obesity properties. However, the molecular mechanisms underlying the inhibitory effects of FX on oxidized low-density lipoprotein (oxLDL)-induced oxidative injuries in human endothelial cells are still largely unknown. This study aims to test the hypothesis that FX protects against oxLDL-induced oxidative stress by upregulating AMP-activated protein kinase (AMPK) and to explore the roles of cAMP response element binding protein (CREB) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).
Human umbilical vein endothelial cells are treated with oxLDL in the presence or absence of FX. FX significantly increases AMPK phosphorylation. In addition, FX diminishes oxLDL-mediated nicotinamide adenine dinucleotide phosphate oxidase activation by inhibiting protein kinase C and subsequently inducing reactive oxygen species generation and impairing the activity of the endogenous antioxidant enzyme superoxidase dismutase. Furthermore, FX restores oxLDL-mediated dephosphorylation of phosphoinositide-3-kinase/Akt and decreases CREB and PGC-1α expression to nearly normal levels. Moreover, FX ameliorates the oxLDL-mediated suppression of mitochondrial function and apoptosis.
These findings provide new insights into the possible molecular mechanisms by which FX mitigates oxLDL-induced endothelial oxidative stress and mitochondrial dysfunction.
动脉粥样硬化性心血管疾病是导致死亡率和发病率最高的疾病。岩藻黄质（FX）具有降血压和抗肥胖的特性。然而，FX 抑制人内皮细胞氧化型低密度脂蛋白（oxLDL）诱导的氧化损伤的分子机制在很大程度上仍然未知。本研究旨在验证 FX 通过上调 AMP 激活蛋白激酶（AMPK）来保护细胞免受 oxLDL 诱导的氧化应激的假设，并探讨 cAMP 反应元件结合蛋白（CREB）和过氧化物酶体增殖物激活受体γ共激活剂-1α（PGC-1α）的作用。
人脐静脉内皮细胞在存在或不存在 FX 的情况下用 oxLDL 处理。FX 显著增加 AMPK 磷酸化。此外，FX 通过抑制蛋白激酶 C 抑制 oxLDL 介导的烟酰胺腺嘌呤二核苷酸磷酸氧化酶激活，随后诱导活性氧生成并损害内源性抗氧化酶超氧化物歧化酶的活性，从而减轻 oxLDL 介导的 NADPH 氧化酶激活。此外，FX 恢复 oxLDL 介导的磷酸肌醇-3-激酶/Akt 去磷酸化，并使 CREB 和 PGC-1α 表达降低至接近正常水平。此外，FX 改善了 oxLDL 介导的线粒体功能和凋亡抑制。
这些发现为 FX 减轻 oxLDL 诱导的内皮氧化应激和线粒体功能障碍的可能分子机制提供了新的见解。
