Prolonged treatment with mevalonolactone induces oxidative stress response with reactive oxygen species production, mitochondrial depolarization and inflammation in human glioblastoma U-87 MG cells

Publication date: Available online 9 May 2018Source: Neurochemistry InternationalAuthor(s): Rossella Gratton, Paola Maura Tricarico, Fulvio Celsi, Sergio CrovellaAbstractMevalonate pathway impairment has been observed in diverse diseases, including Mevalonate Kinase Deficiency (MKD). MKD is a hereditary auto-inflammatory disorder, due to mutations at mevalonate kinase gene (MVK), encoding mevalonate kinase (MK) enzyme. To date, the most accredited MKD pathogenic hypothesis suggests that the typical MKD phenotypes might be due to a decreased isoprenoid production rather than to the excess and accumulation of mevalonic acid, as initially supported. Nevertheless, recent studies provide clear evidences that accumulating metabolites might be involved in MKD pathophysiology by exerting a toxic effect. Our work aims at describing the effects of accumulating mevalonolactone, mostly produced by a dehydration reaction due to mevalonic acid accumulation, using an in vitro cellular model mimicking the glial component of the central nervous system (human glioblastoma U-87 MG cells). In order to mimic its progressive increase, occurring during the disease, U-87 MG cells have been treated repeatedly with growing doses of mevalonolactone, followed by the assessment of oxidative stress response (evaluated by measuring SOD2 and HemeOX expression levels), ROS production, mitochondrial damage and inflammatory response (evaluated by measuring IL1B expression levels). Our results suggest that ...

Source: Neurochemistry International - July 10, 2018 Category: Neuroscience Source Type: research