The vitamin D3 analogue, calcipotriol, induces sphingomyelin hydrolysis in human keratinocytes

FEBS Letters

Orfanos, Constantin E.¹  Geilen, Christoph C.¹  Wieder, Thomas¹  Bektas, Meryem¹ 

[1] Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany

关键词: Calcipotriol;    Sphingomyelin hydrolysis;    Ceramide;    1α;    25-Dihydroxyvitamin D3;    Human keratinocyte;    Signal transduction;    Cell proliferation;    Psoriasis;    C2-ceramide;    N-acetylsphingosine;    cpm;    counts per minute;    HaCaT;    immortalized human keratinocyte cell line;    HL-60;    leukemia cell line;    KBM;    keratinocyte basal medium;    KGM;    keratinocyte growth medium;    MCDB;    cell culture media designed for serum-free growth of specific cell types;    MUH;    4-methylumbelliferyl heptanoate;    NGF;    nerve growth factor;    PBS;    phosphate-buffered saline;    RPMI;    Roswell Park Memorial Institute;    SM;    sphingomyelin;    TNFα;    tumor necrosis factor α;   

DOI  :  10.1016/0014-5793(95)01421-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The possible role of sphingomyelin cycle for the regulation of cell proliferation was investigated in human keratinocytes. The time-dependent breakdown of sphingomyelin was observed in the immortalized human keratinocyte cell line HaCaT as well as in primary human keratinocytes thereby providing evidence that the sphingomyelin cycle might be of importance in the epidermis. Peak levels of 20–30% sphingomyelin hydrolysis were measured 3 h after treatment of the cells with 1α,25-dihydroxyvitamin D₃ or with the vitamin D₃ analogue, calcipotriol. The decrease of sphingomyelin upon addition of vitamin D₃ or calcipotriol was accompanied by an approximately 70% increase of ceramide in the cells. The effects of vitamin D₃ and calcipotriol on sphingomyelin breakdown were paralleled by their antiproliferative potency. Furthermore, the cell-permeable ceramide, N-acetylsphingosine, and natural ceramide inhibited cell proliferation of human keratinocytes. The results presented suggest that induction of the sphingomyelin cycle represents one mechanism mediating the therapeutic effect of calcipotriol in treatment of psoriasis.

【 授权许可】

Unknown