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|Title:||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||Authors:||Keum, Y.-S.
|Keywords:||Butylated hydroxyanisole (BHA)
Mitogen-activated protein kinases (MAPKs)
|Issue Date:||Nov-2006||Citation:||Keum, Y.-S., Han, Y.-H., Liew, C., Kim, J.-H., Xu, C., Yuan, X., Shakarjian, M.P., Chong, S., Kong, A.-N. (2006-11). 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. Pharmaceutical Research 23 (11) : 2586-2594. ScholarBank@NUS Repository. https://doi.org/10.1007/s11095-006-9094-2||Abstract:||Purpose. 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. Methods. 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. Results. 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. Conclusions. 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. © 2006 Springer Science+Business Media, LLC.||Source Title:||Pharmaceutical Research||URI:||http://scholarbank.nus.edu.sg/handle/10635/106045||ISSN:||07248741||DOI:||10.1007/s11095-006-9094-2|
|Appears in Collections:||Staff Publications|
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