Glutathione transferase P silencing promotes neuronal differentiation of retinal R28 cells

Francesca Sciarretta, Chiara Fulci, Camilla Palumbo, Katia Aquilano, Anna Pastore, Egidio Iorio, Daniele Lettieri-Barbato, Rosella Cicconi, Antonella Minutolo, Mariacristina Parravano, Marta Gilardi, Monica Varano, Anna Maria Caccuri

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Abstract

Glutathione transferases (GSTs) play an important role in retinal pathophysiology. Within this family, the GSTP isoform is known as an endogenous regulator of cell survival and proliferation pathways and of cellular responses to oxidative stress. In the present study we silenced GSTP in R28 cells, a retinal precursor cell line with markers of both glial and neuronal origin, and obtained stable clones which were viable and, unexpectedly, characterized by a more neuronal phenotype. The degree of neuronal differentiation was inversely correlated with GSTP residual expression levels. The clone with the lowest expression of GSTP showed metabolic reprogramming, a more favorable redox status and, despite its neuronal phenotype, a sensitivity to glutamate and 4-hydroxynonenal toxicity comparable to that of control cells. Altogether, our evidence shows that near full depletion of GSTP in retinal precursor cells, triggers neuronal differentiation and prosurvival metabolic changes.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusE-pub ahead of print - Feb 11 2019

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Sciarretta, F., Fulci, C., Palumbo, C., Aquilano, K., Pastore, A., Iorio, E., Lettieri-Barbato, D., Cicconi, R., Minutolo, A., Parravano, M., Gilardi, M., Varano, M., & Caccuri, A. M. (2019). Glutathione transferase P silencing promotes neuronal differentiation of retinal R28 cells. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.28246