Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes.
Acrolein, a reactive electrophilic α, β-unsaturated aldehyde, is known to be an alkylating chemical carcinogen. The effect of acrolein on the activation of NF-κB in human malignant epidermal keratinocytes was examined to elucidate the molecular mechanism associated with this NF-κB-acrolein regulation and its consecutive sequence, nitric oxide (NO) production. Acrolein significantly downregulated the cellular NF-κB activity up to 60% compared with control as well as the lipopolysaccharide (LPS)-induced NO production in a dose response manner at concentrations of 10~30 μM. To investigate the regulatory mechanism associated with this NF-κB-acrolein downregulation, the relative level of phosphorylation of I-κBα (serines-32 and -36), a principle regulator of NF-κB activation, represented by acrolein, was quantified. Acrolein inhibited NF-κB activity without altering cellular levels of the phosphorylated and nonphosphorylated forms of I-κBα, implying that the downregulatory effect of acrolein on cellular NF-κB activity in human skin cells is an I-κBα-independent activation pathway. The results suggests that acrolein causes the decrease in nitric oxide production as an I-κBα-independent downregulator of NF-κB activity in human malignant keratinocytes, and acrolein-induced carcinogenesis may be associated with the modulation of cellular NF-κB activity.
Moon
Ki-Young
KY
Department of Clinical Pathology, Gwangju Health College University, Shinchang-Dong, Gwangsan-Gu, Gwangju, Korea. kmoon@ghc.ac.kr
D000171:Acrolein / Q000009:adverse effects*; D000477:Alkylating Agents / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010766:Phosphorylation
D000477:Alkylating Agents; D002273:Carcinogens; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D000171:Acrolein