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

Abstract

Aim of the study: To understand the interaction between oxidative stress and autophagy in gliomas of different grades. Materials and Methods: 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. Results: 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 (<50 years 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. Conclusions: 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.

KEYWORDS: :

• oxidative stress
• gliomas; autophagy
• WHO grading