Downregulation of microsomal glutathione-S-transferase 1 modulates protective mechanisms in differentiated PC12 cells

• Autores: Monika Sobczak, Tomasz Boczek, Antoni Kowalski, Magdalena Wiktorska, Jolanta Niewiarowska, Ludmila Zylinska
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 70, Nº. 2, 2014 (Ejemplar dedicado a: Special Section on the CTP network: Original papers from the 10th meeting of the CTPIOD (Contribution To Progress in Obesity and Diabetes Research), 22th of May 2013, Reus, Spain.), págs. 375-383
• Idioma: inglés
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  • Microsomal glutathione-S-transferase 1 (Mgst1) plays a specific role in protection of cells against oxidative stress. In this study, we assayed the effect of Mgst1 downregulation on cells behavior using differentiated PC12 line, a widely accepted neuronal model system. We have developed stable transfected cells with downregulated Mgst1 (PC12_M), which were differentiated with 1 mM dibutyryl-cAMP (db-cAMP). Mgst1 reduction induced necrosis, decreased ATP amount, and increased thiobarbituric acid reacting substances (TBARS) content. However, in PC12_M cell population, we detected more intensive neuritogenesis than that in mock-transfected cells. Interestingly, total glutathione as well as GSH level were significantly higher than those in control PC12 line. Real-time PCR and Western blot analyses showed elevated expression of enzymes involved in glutathione metabolism�a rate-limiting ?-glutamylcysteine ligase and glutathione reductase. The present study shows for the first time that under stress conditions induced by Mgst1 downregulation, a rescue pathway can be activated and thereby enables differentiated PC12 cells to survive. Since Mgst1expression was reported to decline with age, our results could represent a putative adaptive process during aging. It could also be an early mechanism protecting neuronal cells against some neurodegenerative insults.