Induction of heme oxygenase-1 by plant extract KIOM-79 via Akt pathway and NF-E2 related factor 2 in pancreatic beta-cells.
The objective of the present study was to determine the mechanism by which KIOM-79 induced heme oxygenase-1 (HO-1) in rat pancreatic beta-cells (RINm5F). A mixture of plant extracts (KIOM-79) was obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis. HO-1, an antioxidant phase 2 enzyme, was previously reported to possess cytoprotective properties in pancreatic beta-cells. KIOM-79 induced heme oxygenase-1 (HO-1) expression at the mRNA and protein levels, leading to increased HO-1 activity. The transcription factor, NF-E2 related factor 2 (Nrf2), regulates the antioxidant response element (ARE) of the phase 2 detoxifying and antioxidant enzymes, resulting in modulation of HO-1 expression. KIOM-79 increased nuclear translocation, ARE binding, and transcriptional activity of Nrf2. Furthermore, KIOM-79 also elicited activation of Akt (protein kinase B) and LY294004 (inhibitor of Akt)-suppressed KIOM-79-induced activation of Nrf2, which subsequently decreased HO-1 protein levels. Taken together, these data suggest that KIOM-79 augments the cellular antioxidant defense capacity through induction of HO-1 via the Akt-Nrf2-ARE signaling pathway, thereby protecting cells from streptozotocin-induced oxidative stress.
Kang
Kyoung Ah
KA
College of Medicine, Cheju National University, Jeju-si, Korea.
Kim
Jin Sook
JS
Zhang
Rui
R
Piao
Mei Jing
MJ
Ko
Dong Ok
DO
Wang
Zhi Hong
ZH
Maeng
Young Hee
YH
Eun
Su Yong
SY
Hyun
Jin Won
JW
D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin / Q000037:antagonists & inhibitors* / Q000633:toxicity
C517978:KIOM 79; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010936:Plant Extracts; D013311:Streptozocin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat