Fucoxanthin Protects against oxLDL‐Induced Endothelial Damage via Activating the AMPK‐Akt‐CREB‐PGC1α Pathway
Abstract
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.
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The protective effects of fucoxanthin were attributed to activation of the AMPK-protein kinase C-NOX signaling pathway.
“The protective effects of fucoxanthin were attributed to activation of the AMPK-protein kinase C-NOX signaling pathway.”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [129]
Fucoxanthin alleviated oxidative damage of endothelial cells treated by oxLDL.
“Fucoxanthin, a natural marine carotenoid extracted from edible seaweeds, alleviated oxidative damage of ECs treated by oxLDL.”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [129]
Suppression of oxidative stress blunted activation of the protein kinase B-cyclic AMP-responsive element binding protein-PGC1α pathway, which ameliorated mitochondrial dysfunction and apoptosis.
“Moreover, the suppression of oxidative stress, in turn, blunted the activation of the protein kinase B-cyclic AMP-responsive element binding protein–PGC1α pathway, which ameliorated mitochondrial dysfunction and apoptosis [129].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [129]
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- Authors
- Ou, H., Chou, W., Chu, P., Hsieh, P., Hung, C., & Tsai, K.
- Affiliations
- Asia University (TW)
- National Cheng Kung University (TW)
- China Medical University (TW)
- Corresponding author
- Hung, Ching‐Hsia
- Tsai, Kun‐Ling
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2019-04-10
- Volume
- 63
- Issue
- 10
- Pages
- e1801353-e1801353
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2923522051
- Cited by
- 41
- References
- 49
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 2
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- China Medical University (CMU104‐N‐02)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- fucoxanthin, oxidized LDL, endothelial cells, AMPK, Akt, CREB, PGC-1α, oxidative stress, NADPH oxidase, protein kinase C, superoxide dismutase, mitochondrial dysfunction, apoptosis, atherosclerosis, carotenoids
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Endothelium, Vascular, Humans, Lipoproteins, LDL, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Protective Agents, Xanthophylls, Proto-Oncogene Proteins c-akt, Membrane Potential, Mitochondrial, AMP-Activated Protein Kinases, Human Umbilical Vein Endothelial Cells
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