Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1907785 | Free Radical Biology and Medicine | 2016 | 12 Pages |
Abstract
Cholesterol oxidation products such as oxysterols are considered critical factors in the atherosclerotic plaque formation since they induce oxidative stress, inflammation and apoptotic cell death. 27-hydroxycholesterol (27-OH) is one of the most represented oxysterols in atherosclerotic lesions. We recently showed that relatively low concentrations of 27-OH generated a strong survival signaling through an early and transient increase of cellular ROS level, that enhanced MEK-ERK/PI3K-Akt phosphorylation, in turn responsible of a sustained quenching of ROS production. It remains to identify the link between ERK/Akt up-regulation and the consequent quenching effect on ROS intracellular level that efficiently and markedly delay the pro-apoptotic effect of the oxysterol. Here we report on the potent activation of Nrf2 redox-sensitive transcription factor by low micromolar amount of 27-OH added to U937 promonocytic cells. The 27-OH-exerted induction of Nrf2 and subsequently of the target genes, HO-1 and NQO-1, was proved to be: (i) dependent upon the activation of ERK and Akt pathways, (ii) directly responsible for the quenching of intracellular oxidative stress and by this way (iii) ultimately responsible for the observed oxysterol-induced pro-survival response.
Keywords
HRPHeme oxygenase-1GSRPKCc-Jun NH2-terminal kinaseNQO-1DPIPAGEDAPILXRERKRT-PCRHO-1SERMJnk27-HydroxylasePI3KNOX-2GPXPVDFCYP27A1Nrf2NAC4,6-diamidino-2-phenylindolekeap1ROSSDS–polyacrylamide gel electrophoresispolyvinylidene difluoridediphenyleneiodonium chlorideantioxidant response elementphosphoinositide 3-kinaselow density lipoproteinLDLMEKN-acetyl cysteineAREreverse transcription–polymerase chain reactionHorseradish peroxidaseProtein kinase Cmitogen-activated protein kinaseliver X receptorKinaseextracellular signal-regulated kinaseglutathione reductaseglutathione peroxidaseReactive oxygen species
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Authors
Beyza Vurusaner, Paola Gamba, Simona Gargiulo, Gabriella Testa, Erica Staurenghi, Gabriella Leonarduzzi, Giuseppe Poli, Huveyda Basaga,