UVB upregulates serine palmitoyltransferase in cultured human keratinocytes

Angela Farrell, M. Marek Nagiec, Robert C. Dickson, Peter M. Elias, Walter M. Holleran

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermis is an active site of sphingolipid synthesis, consistent with the role of ceramides as major components of the extracellular bilayers responsible for epidermal permeability barrier integrity. We have shown previously that the enzyme serine palmitoyltransferase (SPT; EC 2.3.1.50), thought to catalyze the rate-limiting step in sphingolipid synthesis, is upregulated in vivo in response both to permeability barrier perturbation and to UVB exposure. However, the molecular mechanisms that regulate SPT activity have not been delineated. The recent isolation of mammalian cDNAs encoding SPT have allowed us to determine whether cultured human keratinocytes express the transcripts for SPT reported in other tissues (i.e., LCB1 and LCB2), and whether UVB-exposure induces alterations in mRNA and/or protein levels for this enzyme. In murine epidermis, increased SPT activity occurs with time following UVB exposure, with a peak increase evident at 48 hrs (3.0- to 4.5-fold increase over non-irradiated controls). In cultured human keratinocytes, a 1.2 - 2.0-fold increase in LCB2 mRNA levels is detected 48 hrs following UVB treatment (23 mJ/cm2) compared to non-irradiated controls. Likewise, the Lcb2 protein level increases following UVB, as shown by Western analysis. These results demonstrate that cultured keratinocytes respond to UVB by increasing both LCB2 mRNA and Lcb2 protein levels, the first demonstration of molecular regulation of this enzyme. These results suggest that the epidermal response to UVB includes upregulation of sphingolipid synthesis at both the mRNA and protein levels. Thus, cultured human keratinocytes represent a useful model for characterizing the molecular regulation of this key enzyme in sphingolipid synthesis.

Original languageEnglish
Pages (from-to)186A
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)

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