Title: A novel mechanism of filaggrin induction and sunburn prevention by ýý-damascenone in Skh-1 mice.
Authors: Uddin, Ahmed N; Labuda, Ivica; Burns, Fredric J
Published In Toxicol Appl Pharmacol, (2012 Dec 15)
Abstract: Understanding how oral administration of aroma terpenes can prevent sunburn or skin cancer in mice could lead to more effective and safer ways of blocking sun damage to human skin. To establish sunburn preventive activity, female Skh-1 mice were given oral ýý-damascenone followed by irradiation with UVR from fluorescent 'sunlamps'. The following endpoints were evaluated versus controls at various times between 1 and 12 days after the terpene: whole genome gene expression and in situ immunohistochemistry of PCNA, keratin 10, filaggrin and caspase 14, and sunburn was evaluated at 5 days. UVR-induced sunburn was prevented by a single oral ýý-damascenone dose as low as 20 ýýL (0.95 mg/g body weight). Microarray analysis showed sunburn prevention doses of ýý-damascenone up-regulated several types of cornification genes, including keratins 1 and 10, filaggrin, caspase 14, loricrin, hornerin and 6 late cornified envelope genes. Immunohistochemical studies of PCNA labeling showed that ýý-damascenone increased the proliferation rates of the following cell types: epidermal basal cells, follicular outer root sheath cells and sebaceous gland cells. Keratin 10 was not affected by ýý-damascenone in epidermis, and filaggrin and caspase 14 were increased in enlarged sebaceous glands. The thickness of the cornified envelope plus sebum layer nearly doubled within 1 day after administration of the ýý-damascenone and remained at or above double thickness for at least 12 days. ýý-Damascenone protected against sunburn by activating a sebaceous gland-based pathway that fortified and thickened the cornified envelope plus sebum layer in a way that previously has been observed to occur only in keratinocytes.
PubMed ID: 22982537
MeSH Terms: Administration, Oral; Animals; Caspase 14/biosynthesis; Caspase 14/genetics; Caspase 14/metabolism; Cell Proliferation/drug effects; Epidermis/cytology; Epidermis/drug effects*; Epidermis/metabolism*; Female; Immunohistochemistry; Intermediate Filament Proteins/biosynthesis*; Intermediate Filament Proteins/genetics; Intermediate Filament Proteins/metabolism; Keratin-10/biosynthesis; Keratin-10/genetics; Keratin-10/metabolism; Mice; Norisoprenoids/administration & dosage; Norisoprenoids/pharmacology*; Oligonucleotide Array Sequence Analysis; Proliferating Cell Nuclear Antigen/biosynthesis; Proliferating Cell Nuclear Antigen/genetics; Proliferating Cell Nuclear Antigen/metabolism; RNA, Messenger/chemistry; RNA, Messenger/genetics; Sunburn/prevention & control*