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.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Wang M,Saw HP,Cui FF,Lin SY,Chang HT,Chiu CD

doi

10.1080/10715762.2018.1504293

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

970-976

issue

9

eissn

1071-5762

issn

1029-2470

journal_volume

52

pub_type

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