pLG72 induces superoxide radicals via interaction and aggregation with SOD1

Abstract

G72 has been characterised as a susceptibility gene that can have wide-ranging effects in a number of neurodegenerative diseases, including schizophrenia and major depression. Indeed, its product, pLG72, is a potential serum biomarker for schizophrenia. Previous transcriptomic and biochemical studies have indicated that pLG72 may induce the production of mitochondrial reactive oxygen species (ROS), resulting in cell damage. Here, we investigated the mechanism of pLG72 by transfecting a human U87 glioblastoma cell line with a G72 construct. By employing ROS-specific scavengers, we discovered that superoxide radicals were specifically induced in the pLG72-expressing cells. We also found that pLG72 interacted and co-localised with superoxide dismutase 1 (SOD1), resulting in aggregation of SOD1 with a concomitant 23% or 74% reduction of total SOD activity, depending on the amount of G72 transfection plasmid. Finally, we found that transfection of U87 cells with the G72 construct caused a 29% decrease in cell proliferation. The observed loss of SOD1 function in pLG72-expressing cells may explain the elevated ROS levels and inhibition of U87 cell proliferation and has implications for understanding the onset of neurodegenerative diseases in humans.

Chlorella vulgaris supplementation effects on performances, oxidative stress and antioxidant genes expression in liver and ovaries of New Zealand White rabbits

“…It is also active against superoxide radical and hydrogen peroxide in both the cytoplasm and mitochondria therefore its up-regulation as result of Chlorella vulgaris supplementation indicated complete cellular protection. Sod1 is also involved in pharmacokinetic and reactive oxygen species detoxification pathways hence the microalga is a drug candidate in development of therapeutic solution for oxidative stress attenuation [51, 52].…”

Biochemical Properties and Physiological Functions of pLG72: Twenty Years of Investigations

“…Increased pLG72 protein levels induced mitochondrial fragmentation (increased number of mitochondria/mm of the dendritic tree along the dendritic shafts) without inducing apoptosis in the COS-7 cell line and primary neurons and changed mitochondrial morphology (the vesicular mitochondria were more mobile, possibly delivered more rapidly to sites of intense growth) and dendritic branching in primary hippocampal neurons (within the period of active dendritogenesis only) [ 38 ]. Interestingly, pLG72 overexpression affected gene expressions of several mitochondrial-related proteins and increased ROS production in U87 glioblastoma cells, a rise quenched by the general ROS quencher Tempol [ 47 ]. The same work reported the co-localization of ectopically expressed pLG72 with superoxide dismutase 1 (SOD1, EC 1.15.1.1), resulting in SOD1 aggregation and partial inactivation, and in decreased cell proliferation.…”

How the Gene NRG1, Erbb4, DAOA, and DISC1 Can Affect the Schizophrenia

“…Recultured plG72 cells were compared with normal cells. The interaction between plG72 and SOD1 was detected by CoralHue fluorescence tracing [13]. It has been found that plG72 can cause SOD1 aggregation and reduce the content of SPD1.…”