Induction of CMV-1 promoter by 4-hydroxy-2-nonenal in human embryonic kidney cells.
Oxidative stress, i.e., excessive production of oxygen free radicals and reactive oxygen species, leads to lipid peroxidation and to formation of reactive aldehydes which act as second messengers of free radicals. It has previously been shown that oxidative stress may be involved in the transcriptional regulation of cytomegalovirus (CMV) immediate early promoter, involved in viral reactivation from latency. In the current study we used a plasmid containing the yellow fluorescent protein (YFP) gene under the control of CMV-1 promoter to monitor the influence of hydrogen peroxide and reactive aldehydes, 4-hydroxy-2-nonenal (HNE) and acrolein, on CMV-1 promoter activation in human embryonic kidney cells (HEK293). While acrolein was ineffective, hydrogen peroxide slightly (50 %) stimulated the CMV promoter. In contrast, HNE had a strong, up to 3-fold, enhancing effect on the CMV-1 promoter within four as well as after 24h of treatment. The most effective was the treatment with 24 microM HNE. This effect of HNE suggests that stressful conditions associated with lipid peroxidation could lead to CMV activation.
Department of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
Morana
M
Jaganjac
Tanja
T
Matijevic
Marina
M
Cindric
Ana
A
Cipak
Lidija
L
Mrakovcic
Wolfgang
W
Gubisch
Neven
N
Zarkovic
D000447:Aldehydes / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000166:cytology; D011401:Promoter Regions, Genetic; D014775:Virus Activation / Q000187:drug effects*
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; C027576:4-hydroxy-2-nonenal