出版社：American Society for Biochemistry and Molecular Biology
摘要：Ceramides (Cers) accumulate within the interstices of the outermostepidermal layers, or stratum corneum (SC), where they representcritical components of the epidermal permeability barrier. Althoughthe SC contains substantial sphingol, indicative of ceramidase(CDase) activity, which CDase isoforms are expressed in epidermisremains unresolved. We hypothesized here that CDase isoformsare expressed within specific epidermal compartments in relationto functions that localize to these layers. Keratinocytes/epidermisexpress all five known CDase isoforms, of which acidic and alkalineCDase activities increase significantly with differentiation,persisting into the SC. Conversely, neutral and phytoalkalineCDase activities predominate in proliferating keratinocytes.These differentiation-associated changes in isoform activity/proteinare attributed to corresponding, differentiation-associatedchanges in mRNA levels (by quantitative RT-PCR). Although fourof the five known CDase isoforms are widely expressed in cutaneousand extracutaneous tissues, alkaline CDase-1 occurs almost exclusivelyin epidermis. These results demonstrate large, differentiation-associated,and tissue-specific variations in the expression and activitiesof all five CDase isoforms. Because alkaline CDase-1 and acidicCDase are selectively upregulated in the differentiated epidermalcompartment, they could regulate functions that localize tothe distal epidermis, such as permeability barrier homeostasisand antimicrobial defense.Supplementary key words ceramide • sphingolipid • sphingosine
Abbreviations: aCDase, acidic ceramidase; alkCDase, alkaline ceramidase; CDase, ceramidase; Cer, ceramide; CHK, cultured human keratinocyte; DIG, digoxigenin; nCDase, neutral ceramidase; phytoCDase, phytoalkaline ceramidase; SC, stratum corneum; SG, stratum granulosum
