NDLI: Induction of Heme Oxygenase-1 (HO-1) and NAD[P]H: Quinone Oxidoreductase 1 (NQO1) by a Phenolic Antioxidant, Butylated Hydroxyanisole (BHA) and Its Metabolite, tert-Butylhydroquinone (tBHQ) in Primary-Cultured Human and Rat Hepatocytes

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Induction of Heme Oxygenase-1 (HO-1) and NAD[P]H: Quinone Oxidoreductase 1 (NQO1) by a Phenolic Antioxidant, Butylated Hydroxyanisole (BHA) and Its Metabolite, tert-Butylhydroquinone (tBHQ) in Primary-Cultured Human and Rat Hepatocytes

Content Provider	Springer Nature Link
Author	Keum, Young Sam Han, Yong Hae Liew, Celine Kim, Jung Hwan Xu, Changjiang Yuan, Xiaoling Shakarjian, Michael P. Chong, Saeho Kong, Ah Ng
Copyright Year	2006
Abstract	This study was aimed to investigate the effects of a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) on the induction of HO-1, NQO1 and Nrf2 proteins and their regulatory mechanisms in primary-cultured hepatocytes.After exposure of BHA and tBHQ to primary-cultured rat and human hepatocytes and mouse neonatal fibroblasts (MFs), Western blot, semi-quantitative RT-PCR and microarray analysis were conducted.Induction of HO-1, NQO1 and Nrf2 proteins and activation of ERK1/2 and JNK1/2 were observed after BHA and tBHQ treatments in primary-cultured rat and human hepatocytes. Semi-quantitative RT-PCR study and microarray analysis revealed that HO-1 and NQO1 were transcriptionally activated in primary-cultured rat hepatocytes and a substantial transcriptional activation, including HO-1 occurred in primary-cultured human hepatocytes after BHA treatment. Whereas BHA failed to induce HO-1 in wild-type and Nrf2 knock-out MFs, tBHQ strongly induced HO-1 in wild-type, but not in Nrf2 knock-out MFs.Our data demonstrate that both BHA and tBHQ are strong chemical inducers of HO-1, NQO1 and Nrf2 proteins in primary-cultured human and rat hepatocytes with the activation of MAPK ERK1/2 and JNK1/2. However, in MFs, BHA failed to induce HO-1, whereas tBHQ strongly induced HO-1 in Nrf2 wild-type but not in Nrf2 knock-out, suggesting that Nrf2 is indispensable for tBHQ-induced HO-1 in MF.
Starting Page	2586
Ending Page	2594
Page Count	9
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	11
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2006-10-18
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	butylated hydroxyanisole (BHA) mitogen-activated protein kinases (MAPKs) Nrf2 tert-butylhydroquinone (tBHQ) Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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