Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Keum, Y.S. et al.

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.

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.[1]

References

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. Keum, Y.S., Han, Y.H., Liew, C., Kim, J.H., Xu, C., Yuan, X., Shakarjian, M.P., Chong, S., Kong, A.N. Pharm. Res. (2006) [Pubmed]

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