Biological response of human diploid keratinocytes to quinone-producing compounds: role of NAD(P)H:quinone oxidoreductase 1.
Reactive oxygen species (ROS) and quinones are known to determine redox balance alteration, oxidative stress and carcinogenicity. Keratinocytes of the human epidermis, a tissue particularly exposed to oxidant stimuli, possess a wide range of antioxidant and detoxifying mechanisms aimed to avoid oxidative damage of the tissue. In the present study, we evaluate the response of diploid and transformed human keratinocytes to exposure to L-dopa and tetrahydropapaveroline (THP), catechol compounds susceptible to undergo oxidation to form quinones with concomitant production of reactive oxygen species. We demonstrated that these compounds elicit up-regulation of intracellular antioxidant enzymes, in a different degree in normal cells with respect to transformed ones. Normal diploid keratinocytes adequately scavenge toxic substances through the activation of several, concurrent pathways. Conversely, in transformed cells, the whole oxidative burden must be detoxified by the limited set of conserved pathways that, accordingly, have to be highly activated. The biological response to catechol toxicity appears to rely on the pathway of NAD(P)H:quinone oxidoreductase 1 (NQO1). In conclusion, NAD(P)H:quinone oxidoreductase 1 confirms its antioxidant and detoxifying role contributing to the capacity of keratinocytes to protect epidermis against oxidative stress. Being retained in almost any cell, it represents a mechanism of general relevance in cell physiology.
Foppoli
Cesira
C
CNR Institute of Molecular Biology and Pathology, c/o Department of Biochemical Sciences, University of Rome "La Sapienza", Piazzale Aldo Moro 5, 00185 Rome, Italy.
De Marco
Federico
F
Blarzino
Carla
C
Perluigi
Marzia
M
Cini
Chiara
C
Coccia
Raffaella
R
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004171:Diploidy; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D011809:Quinones; D012333:RNA, Messenger; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human