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Change in mRNA Expression of Human Cytochrome P450 by Gold Nanoparticles

Keywords: gold nanoparticles , mRNA expression , phase I metabolism , hepatocellular carcinoma cells , Cytochrome P450

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Abstract:

The effect of gold nanoparticles (AuNPs) on the mRNA expression of cytochrome P450 (CYP) enzymes as main metabolizing enzymes has been investigated. Citrate-stabilized AuNPs (AuCi) and polyethyleneimine-stabilized AuNPs (AuPEI) were synthesized and characterized for sizes and surface charges using Transmission Electron Microscopy (TEM) and zeta potential measurement, respectively. The induction effect of AuNPs on mRNA expression of CYPs 1A2, 2C9, 2E1 and 3A4 in human hepatocellular carcinoma (HepG2) cell line was measured with quantitative real time PCR method. The results showed that AuCi and AuPEI had average particle diameters of 15.002.77 and 5.021.81 nm and zeta potential of -40.601.22 and 8.101.59 mV, in orderly. After 48 h exposure to the AuCi (1 and 10 M) and AuPEI (0.1 and 1 M), the CYP1A2 mRNA level in HepG2 cells was over 2-fold induction. Moreover, an addition of 1 M AuPEI to 10 M a-naphthoflavone as CYP1A2 inducer caused the level of CYP1A2 mRNA to be significantly higher (p=0.05) than that induced by a-naphthoflavone alone. The study shows that the mRNA expression change is likely to depend upon the size and charge of AuNPs. The smaller and positively charged AuPEI promote the cellular penetration, thus probably potentiating of CYP mRNA transcription.

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