title: Prolidase-dependent mechanism of (Z)-8,9-epoxyheptadeca-1,11,14-triene-induced inhibition of collagen biosynthesis in cultured human skin fibroblasts.
abstract: The effects of polyolefinic compound from roots of Cirsium palustre, (Z)-8,9-epoxyheptadeca-1,11,14-triene (EHT) on collagen biosynthesis, prolidase activity, expression of insulin-like growth factor receptor (IGF-IR), β1 integrin, MAP kinases (pERK1/2), the transcription factors such as nuclear factor kappa B (NF-κB) and hypoxia-inducible factor-1α (HIF-1α) were evaluated in human dermal fibroblasts treated with micromolar concentrations (40-200 μM) for 24 h. It was found that EHT-dependent inhibition of collagen biosynthesis was accompanied by parallel inhibition in prolidase activity. Since IGF-I is the most potent regulator of both processes and prolidase is regulated by β1 integrin signalling, the effect of EHT on IGF-IR and β1 integrin receptor expressions were evaluated. Exposure of the cells to EHT contributed to distinct increase in IGF-IR and slight increase in β1 integrin receptor expressions. It was accompanied by decrease in expression of pERK1/2, HIF-1α and NF-κB. EHT-dependent inhibition of collagen biosynthesis results from inhibition of prolidase activity, the enzyme involved in collagen biosynthesis.
authors.affiliation: a Department of Medicinal Chemistry , Medical University of Bialystok , Mickiewicza 2d Street, 15-222 Bialystok , Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szoka
authors.affiliation: a Department of Medicinal Chemistry , Medical University of Bialystok , Mickiewicza 2d Street, 15-222 Bialystok , Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Karna
authors.affiliation: b Department of Pharmacognosy , Medical University of Bialystok , Mickiewicza 2a Street, 15-222 Bialystok , Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Nazaruk
authors.affiliation: a Department of Medicinal Chemistry , Medical University of Bialystok , Mickiewicza 2d Street, 15-222 Bialystok , Poland.
authors.forename: Jerzy A
authors.initials: JA
authors.lastname: Palka
mesh_terms: D000475:Alkenes / Q000494:pharmacology; D002478:Cells, Cultured; D031180:Cirsium / Q000737:chemistry; D003094:Collagen / Q000096:biosynthesis*; D004150:Dipeptidases / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D009822:Oils, Volatile / Q000737:chemistry; D010938:Plant Oils / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D011090:Polyenes / Q000494:pharmacology*; D017451:Receptors, Somatomedin / Q000378:metabolism
chemical_list: C000611358:(Z)-8,9-epoxyheptadeca-1,11,14-triene; D000475:Alkenes; D004852:Epoxy Compounds; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019012:Integrin beta1; D016328:NF-kappa B; D009822:Oils, Volatile; D010938:Plant Oils; D011090:Polyenes; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D004150:Dipeptidases; C022449:proline dipeptidase
keywords: (Z)-8,9-epoxyheptadeca-1,11,14-triene; MAP kinases; collagen; hypoxia-inducible factor-1α; insulin-like growth factor receptor; nuclear factor kappa B; prolidase