The effects of serine palmitoyltransferase inhibitor, ISP-I, on UV-induced barrier disruption in the stratum corneum.
We examined the effects of ISP-I (myriocin, thermozymocidin) - a potent inhibitor of serine palmitoyltransferase (SPT) which is involved in the ceramide synthetic pathway-on skin barrier function in post-UVB-irradiated hairless mouse skin. Disruption of the skin barrier function after UVB irradiation as represented by the increase in transepidermal water loss (TEWL) was significantly suppressed with ISP-I treatment. In the ISP-I-treated skin, the peak of cell proliferation was observed 24 h earlier than in vehicle-treated skin. In addition, the number of apoptotic cells in ISP-I-treated skin showed a sharp decrease at 48 and 72 h post-irradiation. The number of stratum corneum cell layers was increased in ISP-I-treated skin at 72 h after UVB irradiation; at this time, TEWL in ISP-I-treated skin was lower than that in the vehicle-treated skin. We suggest ISP-I treatment altered cell proliferation and apoptosis after UVB exposure by modulating ceramide synthesis in epidermal cells, resulting in an increase of stratum corneum layers which lessened the effects of irradiation-induced barrier disruption.
POLA Chemical Industries, Inc., Yokohama, Japan. k-mizukoshi@pola.co.jp
Koji
K
Mizukoshi
Hiroshi
H
Oshima
Katsuo
K
Matsumoto
Ryouji
R
Hirose
Tetsuro
T
Fujita
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001203:Ascomycota / Q000737:chemistry*; D001688:Biological Products / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002518:Ceramides / Q000096:biosynthesis; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000528:radiation effects; D005229:Fatty Acids, Monounsaturated / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D051102:Serine C-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D014867:Water
D001688:Biological Products; D002518:Ceramides; D005229:Fatty Acids, Monounsaturated; D014867:Water; D051102:Serine C-Palmitoyltransferase; C001996:thermozymocidin