Permeability barrier disruption increases the level of serine palmitoyltransferase in human epidermis.
Sphingolipids play an important role in the homeostasis and barrier function of human stratum corneum. A disturbance of sphingolipid formation is supposed to be a crucial factor for the increased transepidermal water loss in common skin diseases like atopic eczema or psoriasis. The key enzyme for de novo sphingolipid synthesis is serine palmitoyltransferase, which consists of two different subunits, named LCB1 and LCB2 proteins. In order to investigate the induction of LCB2 synthesis in human epidermis, skin barrier disruption was performed by tape stripping on the forearm of healthy volunteers enough to obtain a 3-4-fold increase in transepidermal water loss. Skin punch biopsies were taken before and 0.5, 2, 4, and 8 h after tape stripping by each volunteer to measure LCB2 at the mRNA level. Additional biopsies taken before and 12 h after tape stripping were used to evaluate LCB2 at the protein level. Our results show that 0.5 and 2 h after tape stripping the LCB2 mRNA expression was decreased compared to control in all cases. A significant increase in LCB2 mRNA expression was detectable 4 h after barrier disruption, with individual variations; no further increase was detectable 8 h after tape stripping. Immunohistochemical analysis 12 h after barrier disruption showed increased LCB2 immunolocalization in the inner epidermis, whereas in the outer epidermis it was similar to control. LCB2 mRNA expression preceded the expression of the corresponding protein by 4-8 h. Our findings support the concept that an increase in transepidermal water loss is an obligatory trigger for the upregulation of serine palmitoyltransferase mRNA expression in humans.
Stachowitz
Silke
S
Department of Dermatology and Allergy Biederstein, Technical University Munich, Germany.
Alessandrini
Francesca
F
Abeck
Dietrich
D
Ring
Johannes
J
Behrendt
Heidrun
H
D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D004817:Epidermis / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051102:Serine C-Palmitoyltransferase; D014867:Water / Q000378:metabolism
D012333:RNA, Messenger; D014867:Water; D000217:Acyltransferases; C495089:SPTLC2 protein, human; D051102:Serine C-Palmitoyltransferase