title: Vitamin C Stimulates Epidermal Ceramide Production by Regulating Its Metabolic Enzymes.
abstract: Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C (50 μg/ml) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolic-related enzymes, and as a result, could improve overall epidermal barrier function.
authors.affiliation: Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Kun Pyo
authors.initials: KP
authors.lastname: Kim
authors.affiliation: College of Pharmacy and MRC, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Kyong-Oh
authors.initials: KO
authors.lastname: Shin
authors.affiliation: Department of Dermatology, Northern California Institute for Research and Education (NCIRE)-VA Medical Center, University of California, San Francisco (UCSF), San Francisco, California 94158, USA.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: Nova Southeastern College of Medicine, Fort Lauderdale, Florida 33314, USA.
authors.forename: Shivtaj
authors.initials: S
authors.lastname: Mann
authors.affiliation: College of Pharmacy and MRC, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Yong Moon
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Yunhi
authors.initials: Y
authors.lastname: Cho
keywords: Calcium; Ceramide; Ceramide metabolic enzymes; Epidermal barrier; Keratinocyte differentiation; Vitamin C