Triphlorethol-A induces heme oxygenase-1 via activation of ERK and NF-E2 related factor 2 transcription factor.
Triphlorethol-A, phlorotannin found in Ecklonia cava, induced heme oxygenase-1 (HO-1) expression at mRNA and protein levels, leading to increased HO-1 activity. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase 2 detoxifying and antioxidant enzymes. Triphlorethol-A increased nuclear translocation, ARE binding, and transcriptional activity of Nrf2. Triphlorethol-A exhibited activation of ERK and U0126, inhibitor of ERK kinase, suppressed triphlorethol-A induced activation of Nrf2, finally decreased HO-1 protein level. Taken together, these data suggest that triphlorethol-A augments cellular antioxidant defense capacity through induction of HO-1 via ERK-Nrf2-ARE signaling pathway, thereby protecting cells from oxidative stress.
Kang
Kyoung Ah
KA
Department of Biochemistry, College of Medicine and Applied Radiological Science Research Institute, Cheju National University, Jeju 690-756, Republic of Korea.
Lee
Kyoung Hwa
KH
Park
Jae Woo
JW
Lee
Nam Ho
NH
Na
Hye Kyung
HK
Surh
Young Joon
YJ
You
Ho Jin
HJ
Chung
Myung Hee
MH
Hyun
Jin Won
JW
D000818:Animals; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; C504400:triphlorethol-A; D010696:Phloroglucinol; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases