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.

• Authors: Minxue Lian, Xiaodong Zhang, Hui Wang, Hao Liu, Wei Chen, Shiwen Guo
• Journal: The International journal of neuroscience (Int J Neurosci) Vol. 124 Issue 12 Pg. 926-34 (Dec 2014) ISSN: 1563-5279 [Electronic] England
• PMID: 24617962 (Publication Type: Journal Article)

Chemical References

• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Adult
• Aged
• Autophagy (physiology)
• Brain Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Deoxyguanosine (analogs & derivatives, biosynthesis)
• Female
• Glioma (metabolism, pathology)
• Humans
• Male
• Middle Aged
• Oxidative Stress (physiology)
• Young Adult