Arachidonate 12-lipoxygenase inhibitors promote S100A3 citrullination in cultured SW480 cells and isolated hair follicles

Abstract

The human hair shaft is covered with multiple scale-like cuticular layers. During the terminal differentiation stage of immature cuticular cells within the hair follicle, cysteine-rich calcium binding S100A3 protein is predominantly translated, and its arginine residues are converted to citrullines by peptidylarginine deiminases (PADI). In this study, we found several naturally occurring compounds (e.g., hinokitiol, escletin, and quercetin) elevate S100A3 citrullination in a human colorectal adenocarcinoma cell line (SW480). Selected compounds similarly promoted cuticular differentiation within isolated human hair follicles. Their promotive activities correlated with the previously reported inhibitory activities of arachidonate 12-lipoxygenase (ALOX12) in vitro. Microarray analysis revealed that ALOX12 inhibitor remarkably up-regulated heparin-binding epidermal growth factor-like growth factor (HBEGF). ALOX12 inhibitor and recombinant HBEGF similarly regulated expression of PADI genes in SW480 cells. In isolated hair follicles, arachidonic acid strongly promoted S100A3 citrullination along with elevation of HBEGF. These results suggest that ALOX12 inhibition efficiently triggers hair cuticle maturation by modulating arachidonate metabolism in concert with HBEGF.