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

Hsiu Chung Ou, Wan Ching Chou, Pei Ming Chu, Pei Ling Hsieh, Ching-Hsia Hung, Kun-Ling Tsai

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1801353
JournalMolecular Nutrition and Food Research
Volume63
Issue number10
DOIs
Publication statusPublished - 2019 May 1

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AMP-activated protein kinase
Cyclic AMP Response Element-Binding Protein
AMP-Activated Protein Kinases
response elements
low density lipoprotein
binding proteins
oxidative stress
Oxidative Stress
antihypertensive agents
dephosphorylation
phosphatidylinositol 3-kinase
protein kinase C
oxidized low density lipoprotein
fucoxanthin
NADP (coenzyme)
animal injuries
1-Phosphatidylinositol 4-Kinase
cardiovascular diseases
endothelial cells
morbidity

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

Cite this

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title = "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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Fucoxanthin Protects against oxLDL-Induced Endothelial Damage via Activating the AMPK-Akt-CREB-PGC1α Pathway. / Ou, Hsiu Chung; Chou, Wan Ching; Chu, Pei Ming; Hsieh, Pei Ling; Hung, Ching-Hsia; Tsai, Kun-Ling.

In: Molecular Nutrition and Food Research, Vol. 63, No. 10, 1801353, 01.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fucoxanthin Protects against oxLDL-Induced Endothelial Damage via Activating the AMPK-Akt-CREB-PGC1α Pathway

AU - Ou, Hsiu Chung

AU - Chou, Wan Ching

AU - Chu, Pei Ming

AU - Hsieh, Pei Ling

AU - Hung, Ching-Hsia

AU - Tsai, Kun-Ling

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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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