Upregulation of heme oxygenase-1 by brazilin via the phosphatidylinositol 3-kinase/Akt and ERK pathways and its protective effect against oxidative injury.
Heme oxygenase (HO)-1 is a cytoprotective enzyme that is activated by various phytochemicals. We examined the ability of brazilin to upregulate HO-1 expression in auditory cells. We found that brazilin induced the expressions of HO-1 mRNA and protein in concentration- and time-dependent manners. Brazilin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated brazilin-induced expression of HO-1. Brazilin induced a temporary increase in the phosphorylation of Akt. While LY294002, a non-selective phosphotidylinositol 3-kinase (PI3K) inhibitor, was able to reduce brazilin-induced phosphorylation of Akt and the subsequent induction of HO-1. Brazilin activated the extracellular signal-regulated kinase (ERK) and p38 pathways, and the ERK pathway played an important role in HO-1 expression. Brazilin protected the cells against t-butyl hydroperoxide (t-BHP)-induced cell death. The protective effect of brazilin was abrogated by anti-sense oligodeoxynucleotides (ODN) against the HO-1 gene. These results demonstrate that the expression of HO-1 by brazilin is mediated via the PI3K/Akt and ERK pathways, and this expression inhibits t-BHP-induced cell death in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells.
Choi
Byung-Min
BM
Vestibulocochlear Research Center and Department of Biochemistry, School of Medicine, Wonkwang University, Iksan, Chonbuk 570-749, Republic of Korea.
Kim
Bok-Ryang
BR
D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001578:Benzopyrans; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C044362:brazilin