Fucoxanthin Protects against oxLDL-Induced Endothelial Damage via Activating the AMPK-Akt-CREB-PGC1α Pathway.

Abstract

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.