Cytoprotective effect of eckol against oxidative stress-induced mitochondrial dysfunction: involvement of the FoxO3a/AMPK pathway.
This study investigated the cytoprotective effect of Ecklonia cava-derived eckol against H2O2-induced mitochondrial dysfunction in Chang liver cells. While H2O2 augmented levels of mitochondrial reactive oxygen species (ROS), eckol decreased it. Eckol also attenuated high intracellular Ca(2+) levels stimulated by H2O2 and recovered H2O2-diminished ATP levels and succinate dehydrogenase activity. Eckol time-dependently increased the expression of manganese superoxide dismutase (Mn SOD), a mitochondrial antioxidant enzyme with cytoprotective effect against oxidative stress. Eckol recovered Mn SOD expression and activity that were decreased by H2O2. Finally, eckol induced Mn SOD through phosphorylated AMP-activated protein kinase (AMPK) and forkhead box O3a (FoxO3a). Specific silencing RNAs (siRNAs) against FoxO3a and AMPK reduced eckol-stimulated Mn SOD expression, and diethyldithiocarbamate (Mn SOD inhibitor) and siRNA against Mn SOD reduced the cytoprotective effect of eckol against H2O2-provoked cell death. These results demonstrate that eckol protects cells from mitochondrial oxidative stress by activating AMPK/FoxO3a-mediated induction of Mn SOD.
School of Medicine, Jeju National University, Jeju, 690-756, Korea.
Areum Daseul
AD
Kim
Kyoung Ah
KA
Kang
Mei Jing
MJ
Piao
Ki Cheon
KC
Kim
Jian
J
Zheng
Cheng Wen
CW
Yao
Ji Won
JW
Cha
Chang Lim
CL
Hyun
Hee Kyoung
HK
Kang
Nam Ho
NH
Lee
Jin Won
JW
Hyun
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D019610:Cytoprotection; D004147:Dioxins / Q000008:administration & dosage*; D004050:Ditiocarb / Q000008:administration & dosage; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000378:metabolism
D000975:Antioxidants; D004147:Dioxins; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C060311:eckol; D004050:Ditiocarb; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D055372:AMP-Activated Protein Kinases
AMP-ACTIVATED PROTEIN KINASE; CYTOPROTECTION; ECKOL; FORKHEAD BOX O3a; MANGANESE SUPEROXIDE DISMUTASE