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The International journal of neuroscience

Increased 8-hydroxydeoxyguanosine in high-grade gliomas is associated with activation of autophagy.


PMID 24617962

Abstract

To understand the interaction between oxidative stress and autophagy in gliomas of different grades. In the present study, we analyzed levels of oxidative stress in 45 human glioma tumors, using the DNA oxidation marker 8-hydroxydeoxyguanosine (8-OHdG). In addition, we determined activation of autophagy in gliomas samples by assessing expression of microtubule-associated protein 1 light chain-3B (LC3B). To confirm our in vivo findings, in vitro studies using U87 cells were conducted. It was determined that the grade of gliomas, that is, different malignant degrees according to WHO classification, significantly affected level of 8-OHdG. High levels of 8-OHdG were present in high-grade gliomas. This trend was significant in male patients and in young adult patients (<50xa0years old). Further study showed increased expression of LC3B in high-grade gliomas. In addition, levels of 8-OHdG and expression of LC3B were positively correlated. Reducing autophagic activity by 3-methyladenine resulted in significantly increased intracellular reactive oxygen species (ROS) in U87 cells. Our study provides evidence that high levels of oxidative stress in high-grade gliomas are associated with autophagy activation that may play a protective role promoting the survival of high-grade gliomas under severe oxidative stress.