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Fucoxanthin Protects against oxLDL‐Induced Endothelial Damage via Activating the AMPK‐Akt‐CREB‐PGC1α Pathway
Author(s) -
Ou HsiuChung,
Chou WanChing,
Chu PeiMing,
Hsieh PeiLing,
Hung ChingHsia,
Tsai KunLing
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201801353
Subject(s) - creb , protein kinase a , ampk , protein kinase b , oxidative stress , nicotinamide adenine dinucleotide phosphate , chemistry , reactive oxygen species , endothelial dysfunction , endocrinology , microbiology and biotechnology , medicine , phosphorylation , biochemistry , biology , oxidase test , transcription factor , enzyme , gene
Scope 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). Methods and Results 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. Conclusion These findings provide new insights into the possible molecular mechanisms by which FX mitigates oxLDL‐induced endothelial oxidative stress and mitochondrial dysfunction.