Increased monoamine oxidase A activity in the epidermis of patients with vitiligo

Abstract

Human keratinocytes under in vitro conditions synthesize norepinephrine and epinephrine, whereas melanocytes lack this capacity. Keratinocytes established from lesional and nonlesional skin of patients with vitiligo synthesized four and two times more norepinephrine, respectively, than controls. Epinephrine synthesis was similar in keratinocytes from uninvolved epidermis and controls, but cells from involved skin had 6.5-fold less epinephrine than controls, indicative of low phenylehtanolamine-N-methyl transferase (PNMT) activity. Similar results were obtained in five patients with vitiligo who showed low epinephrine levels in involved epidermis. Both human keratinocytes and melanocytes expressed significant levels of monoamine oxidase A (MAO-A) activities as shown using 14C-labelled 5-hydroxytryptamine as substrate and immunohistochemical staining with mouse monoclonal antibody. MAO-A activities in the total epidermis of patients with vitiligo were increased five- to ten-fold compared with skin of type-matched controls. Similar increases in MAO-A activities were also found in both keratinocytes and melanocytes established in vitro from vitiliginous epidermis. Based on these results, it can be concluded that defective catecholamine synthesis in the epidermis of patients with vitiligo leads to increased levels of norepinephrine with a concomitant increase in MAO-A activity.