Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes

• Published in: Archives of toxicology 2011-05, Vol.85 (5), p.499-504
• Main Author: Moon, Ki-Young
• Format: Article
• Language: English
• Subjects: Acrolein - adverse effects; Alkylating Agents - metabolism; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - metabolism; Cell Line, Tumor; Chemical agents; Down-Regulation; Environmental Health; Epidermis - cytology; Epidermis - drug effects; Humans; I-kappa B Proteins - genetics; I-kappa B Proteins - metabolism; Keratinocytes - drug effects; Keratinocytes - metabolism; Lipopolysaccharides - metabolism; Medical sciences; Molecular Toxicology; NF-kappa B - drug effects; NF-kappa B - genetics; NF-kappa B - metabolism; Nitric Oxide - biosynthesis; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Phosphorylation; Toxicology; Tumors
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-010-0599-4

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.