Human Papilloma Virus Type 16 E7 Genes Protect Astrocytes against Apoptotic and Necrotic Death Induced by Hydrogen Peroxide .
10.3349/ymj.2001.42.5.471
- Author:
Won Tack LEE
1
;
Jong Eun LEE
;
Sung Ho LEE
;
Hyun Sook JANG
;
Rona G GIFFARD
;
Kyung Ah PARK
Author Information
1. Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea. kapark@yumc.yonsei.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
E6 gene
- MeSH:
Animal;
Apoptosis/*physiology;
Astrocytes/*drug effects/pathology/*physiology;
Cells, Cultured;
Hydrogen Peroxide/*pharmacology;
Mice;
Necrosis;
Oncogene Proteins, Viral/*genetics/*physiology;
Oxidants/*pharmacology;
Signal Transduction/physiology
- From:Yonsei Medical Journal
2001;42(5):471-479
- CountryRepublic of Korea
- Language:English
-
Abstract:
Hydrogen peroxide is considered to be a dose- and time-dependent mediator in apoptotic and necrotic death. In this study, we examined the signaling of the E6 and E7 proteins with respect to apoptosis or necrosis after H2O2 injury using an in vitro model with overexpressed E6 or E7 genes. For this purpose, the E6 and E7 gene expressing astrocytes were exposed to 0.01 mM and 0.2 mM H2 O2 solutions. Twenty- four hours after treatment with the lower dosage(0.01 mM H2O2), control, E6-expressing cells suffered about 45% injury and LXSN-expressi ng cells decreased by 67% as assessed by LDH release. However, E7-expressing cells showed less injury, resulting in 20-30% of LDH release. Astrocytes expressing E6, E7, LXSN and mock-infected cells showed a typical apoptotic death patter n on the DNA gel after treatment with a low-dose of H2O2 (0.01 mM), however the y died from necrotic death after a high-dose (0.2 mM) H2O2. Overexpression of HPV-E7 genes protected the cells from apoptotic death after a low-dose of H2O2 and from necrotic death after a high-dose of H2O2, while the overexpression of E 6 genes from the necrotic death. E7 expressing astrocytes showed higher catalas e activity and the levels of E2F protein surged more than 100-folds compared with the control astrocytes. We believe that the activity of E7 protein to protect astrocytes from H2O2 injury was at least partly due to increased catalase, a scavenger protein.
