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Open AccessArticle
Exploring the Regulation of Cytochrome P450 in SH-SY5Y Cells: Implications for the Onset of Neurodegenerative Diseases
by
Alice Pifferi
Alice Pifferi 1,
Elda Chiaino
Elda Chiaino 1,
Jesus Fernandez-Abascal
Jesus Fernandez-Abascal 2,3
,
Aoife C. Bannon
Aoife C. Bannon 1,
Gavin P. Davey
Gavin P. Davey 4
,
Maria Frosini
Maria Frosini 1,*
and
Massimo Valoti
Massimo Valoti 1
1
Dipartimento di Scienze della Vita, Università di Siena, viale A. Moro 2, 53100 Siena, Italy
2
Andalusian Centre for Developmental Biology (CABD), CSIC-Universidad Pablo de Olavide-Junta de Andalucía, Carretera de Utrera km 1, 41013 Sevilla, Spain
3
Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Carretera de Utrera km 1, 41013 Seville, Spain
4
. School of Biochemistry and Immunology, Trinity College Dublin, 3533645 Dublin, Ireland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(13), 7439; https://doi.org/10.3390/ijms25137439 (registering DOI)
Submission received: 20 March 2024
/
Revised: 24 June 2024
/
Accepted: 28 June 2024
/
Published: 6 July 2024
Abstract
Human individual differences in brain cytochrome P450 (CYP) metabolism, including induction, inhibition, and genetic variation, may influence brain sensitivity to neurotoxins and thus participate in the onset of neurodegenerative diseases. The aim of this study was to explore the modulation of CYPs in neuronal cells. The experimental approach was focused on differentiating human neuroblastoma SH-SY5Y cells into a phenotype resembling mature dopamine neurons and investigating the effects of specific CYP isoform induction. The results demonstrated that the differentiation protocols using retinoic acid followed by phorbol esters or brain-derived neurotrophic factor successfully generated SH-SY5Y cells with morphological neuronal characteristics and increased neuronal markers (NeuN, synaptophysin, β-tubulin III, and MAO-B). qRT-PCR and Western blot analysis showed that expression of the CYP 1A1, 3A4, 2D6, and 2E1 isoforms was detectable in undifferentiated cells, with subsequent increases in CYP 2E1, 2D6, and 1A1 following differentiation. Further increases in the 1A1, 2D6, and 2E1 isoforms following β-naphthoflavone treatment and 1A1 and 2D6 isoforms following ethanol treatment were evident. These results demonstrate that CYP isoforms can be modulated in SH-SY5Y cells and suggest their potential as an experimental model to investigate the role of CYPs in neuronal processes involved in the development of neurodegenerative diseases.
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MDPI and ACS Style
Pifferi, A.; Chiaino, E.; Fernandez-Abascal, J.; Bannon, A.C.; Davey, G.P.; Frosini, M.; Valoti, M.
Exploring the Regulation of Cytochrome P450 in SH-SY5Y Cells: Implications for the Onset of Neurodegenerative Diseases. Int. J. Mol. Sci. 2024, 25, 7439.
https://doi.org/10.3390/ijms25137439
AMA Style
Pifferi A, Chiaino E, Fernandez-Abascal J, Bannon AC, Davey GP, Frosini M, Valoti M.
Exploring the Regulation of Cytochrome P450 in SH-SY5Y Cells: Implications for the Onset of Neurodegenerative Diseases. International Journal of Molecular Sciences. 2024; 25(13):7439.
https://doi.org/10.3390/ijms25137439
Chicago/Turabian Style
Pifferi, Alice, Elda Chiaino, Jesus Fernandez-Abascal, Aoife C. Bannon, Gavin P. Davey, Maria Frosini, and Massimo Valoti.
2024. "Exploring the Regulation of Cytochrome P450 in SH-SY5Y Cells: Implications for the Onset of Neurodegenerative Diseases" International Journal of Molecular Sciences 25, no. 13: 7439.
https://doi.org/10.3390/ijms25137439
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