title: Alteration of mRNA levels of delta-aminolevulinic acid synthase, ferrochelatase and heme oxygenase-1 in griseofulvin induced protoporphyria mice.
abstract: Human erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism and its experimental murine model can be produced by treatment with griseofulvin (GF). We investigated the alteration of mRNA expression in ferrochelatase (FeC), delta-aminolevulinic acid synthase (ALAS) and heme oxygenase-1 (HO-1) in liver, skin and peripheral blood cells of GF-treated mice. In liver, ALAS mRNA was enhanced dramatically by GF administration, in accord with thesis that the expression of ALAS is regulated by feedback mechanism. The expression of HO-1 mRNA increased most rapidly and drastically in liver, however its mechanism of regulation may be different from that of ALAS mRNA. The level of FeC mRNA in liver was less affected with GF treatment. Our results indicate that the inhibition of FeC by GF administration might occur primarily at post-transcriptional level. Similar effects were observed in the ALAS and HO-1 mRNA expression in peripheral blood cells, 2-fold increase in the ALAS mRNA and increase from undetectable level to detectable level in the HO-1 mRNA. In skin of GF-treated mice, average increases of 1.3-fold in the ALAS mRNA and 1.6-fold in the HO-1 mRNA were statistically insignificant. The FeC mRNA level was not altered in peripheral blood or in skin of GF-treated mice. The present study indicates that the molecular analysis is practicable in skin and peripheral blood. In further study, this model could contribute to investigate the pathogenesis of clinical manifestation including possibly cutaneous changes in EPP.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inafuku
authors.forename: A
authors.initials: A
authors.lastname: Takamiyagi
authors.forename: M
authors.initials: M
authors.lastname: Oshiro
authors.forename: T
authors.initials: T
authors.lastname: Kinjo
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.forename: S
authors.initials: S
authors.lastname: Nonaka
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000235:genetics; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects / Q000201:enzymology; D004798:Enzymes / Q000235:genetics*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005294:Ferrochelatase / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006118:Griseofulvin / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D007501:Iron / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D017121:Porphyria, Hepatoerythropoietic / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D011485:Protein Binding; D011524:Protoporphyrins / Q000097:blood; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D004798:Enzymes; D008565:Membrane Proteins; D011524:Protoporphyrins; D012333:RNA, Messenger; D014168:Transferrin; D006118:Griseofulvin; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D000624:5-Aminolevulinate Synthetase; D005294:Ferrochelatase