The E6 and E7 genes of human papilloma virus-type 16 protect primary astrocyte cultures from injury.
Many oncogenes are implicated in the regulation of apoptosis as well as in control of the cell cycle, and several have been shown to protect cells from injury. We tested whether the expression of human papillomavirus type 16 genes E6 and E7 could protect primary astrocytes from injury. Retroviral vectors were used to express E6, E7, or E6E7 in primary murine astrocyte cultures. Astrocytes expressing E6E7 suffered less than half the injury seen in controls after exposure to 400 microM H2O2. When we compared astrocytes expressing only E6 or E7, cells expressing E7 alone were protected to a greater extent and from more severe injury than those expressing E6. E6E7, E6 and E7 all provided protection from 30 h glucose deprivation, but again E7 provided the best protection, reducing injury to less than a third of that seen in controls. Expression of E7 alone decreases vulnerability to both hydrogen peroxide and glucose deprivation injury while E6 alone primarily decreases glucose deprivation injury. These results demonstrate that expression of human papillomavirus oncogenes can reduce the vulnerability of astrocytes to oxidative stress and nutrient deprivation.
Lee
J E
JE
Department of Anesthesia, Stanford University, Stanford, CA 94305, USA.
Kim
C Y
CY
Giaccia
A J
AJ
Giffard
R G
RG
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000201:enzymology / Q000821:virology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D015344:DNA Probes, HPV; D015967:Gene Expression Regulation, Viral; D005947:Glucose / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007003:Hypoglycemia / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins
D015344:DNA Probes, HPV; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D016877:Oxidants; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005947:Glucose