Premium
Identification of the human sphingolipid C4‐hydroxylase, hDES2, and its up‐regulation during keratinocyte differentiation
Author(s) -
Mizutani Yukiko,
Kihara Akio,
Igarashi Yasuyuki
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00274-1
Subject(s) - sphingolipid , identification (biology) , microbiology and biotechnology , keratinocyte , chemistry , biochemistry , biology , computational biology , in vitro , botany
The C4‐hydroxylation of dihydrosphingosine or dihydroceramide is a key reaction in the biosynthesis of phytosphingolipids, both in yeasts and in mammalian cells. Mouse DES2 (mDES2) was recently cloned and shown to work as a Δ4‐desaturase/C4‐hydroxylase, when expressed in yeast cells. Here, we cloned a human homologue of mDES2, hDES2, by homology search utilizing a BLAST program. When expressed in HEK 293 cells, hDES2 exhibited hydroxylase activity for dihydroceramide. Northern blot analyses of hDES2 revealed high expression in skin, intestines, and kidney, sites reportedly possessing high levels of phytosphingolipids. Furthermore, up‐regulation of hDES2 mRNA expression and subsequent phytoceramide production were observed during vitamin C/serum‐induced differentiation of human keratinocytes. These results suggest that the newly cloned hDES2 plays an essential role in phytosphingolipid synthesis in human skin and other phytosphingolipid‐containing tissues.