β-Naphtoflavone and Ethanol Induce Cytochrome P450 and Protect towards MPP+ Toxicity in Human Neuroblastoma SH-SY5Y Cells

• Published in: International journal of molecular sciences Vol. 19; no. 11; p. 3369
• Main Authors: Fernandez-Abascal, Jesus, Ripullone, Mariantonia, Valeri, Aurora, Leone, Cosima, Valoti, Massimo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.10.2018; MDPI
• Subjects: Brain; Cytochrome; Dopamine; Drug interactions; Ethanol; Liver; Metabolism; Neuroblastoma; Neurodegeneration; Parkinson's disease; Proteins; Toxicity; mitochondrial localization; cytochrome P450 enzyme system; xenobiotic toxicity; cytochrome P450 induction; Parkinson’s disease; neurodegeneration and neuroprotection
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19113369

Cytochrome P450 (CYP) isozymes vary their expression depending on the brain area, the cell type, and the presence of drugs. Some isoforms are involved in detoxification and/or toxic activation of xenobiotics in central nervous system. However, their role in brain metabolism and neurodegeneration is still a subject of debate. We have studied the inducibility of CYP isozymes in human neuroblastoma SH-SY5Y cells, treated with β-naphtoflavone (β-NF) or ethanol (EtOH) as inducers, by qRT-PCR, Western blot (WB), and metabolic activity assays. Immunohistochemistry was used to localize the isoforms in mitochondria and/or endoplasmic reticulum (ER). Tetrazolium (MTT) assay was performed to study the role of CYPs during methylphenyl pyridine (MPP+) exposure. EtOH increased mRNA and protein levels of CYP2D6 by 73% and 60% respectively. Both β-NF and EtOH increased CYP2E1 mRNA (4- and 1.4-fold, respectively) and protein levels (64% both). The 7-ethoxycoumarin O-deethylation and dextromethorphan O-demethylation was greater in treatment samples than in controls. Furthermore, both treatments increased by 22% and 18%, respectively, the cell viability in MPP+-treated cells. Finally, CYP2D6 localized at mitochondria and ER. These data indicate that CYP is inducible in SH-SY5Y cells and underline this in vitro system for studying the role of CYPs in neurodegeneration.