1,2,3,4,6-penta-O-galloyl-beta-D-glucose up-regulates heme oxygenase-1 expression by stimulating Nrf2 nuclear translocation in an extracellular signal-regulated kinase-dependent manner in HepG2 cells.
OBJECTIVE
To examine the potency of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) as a hepatic heme oxygenase-1 (HO-1) inducer and its regulation in HepG2 cells.


METHODS
Expression of HO-1 and NF-E2-related factor 2 (Nrf2) and activation of mitogen-activated protein (MAP) kinases were analyzed by Western blot, immunofluorescence assay, and flow cytometry. Transfections of HO-1 gene, small interfering RNAs for HO-1 and Nrf2, and dominant-negative gene for MAP/extracellular signal-regulated kinase (ERK) were carried out to dissect the signaling pathways leading to HO-1 expression in HepG 2 cells.


RESULTS
PGG up-regulated HO-1 expression and this expression conferred cytoprotection against oxidative injury induced by t-butyl hydroperoxide. Moreover, PGG induced Nrf2 nuclear translocation, which was found to be an upstream step of PGG-induced HO-1 expression, and ERK activation, of which pathway was involved in PGG-induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection.


CONCLUSIONS
PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK-dependent manner, and HO-1 expression by PGG may serve as one of the important mechanisms for its hepatoprotective effects.
Pae
Hyun-Ock
HO
Medicinal Resources Research Institute, Wonkwang University, Iksan-Shi, Chonbug, 570-749, Republic of Korea.
Oh
Gi-Su
GS
Jeong
Sun-Oh
SO
Jeong
Gil-Saeng
GS
Lee
Bok-Soo
BS
Choi
Byung-Min
BM
Lee
Ho-Sub
HS
Chung
Hun-Taeg
HT
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D019610:Cytoprotection; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000235:genetics*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D015854:Up-Regulation
D047348:Hydrolyzable Tannins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C435084:pentagalloylglucose; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases