Prolidase-dependent mechanism of (Z)-8,9-epoxyheptadeca-1,11,14-triene-induced inhibition of collagen biosynthesis in cultured human skin fibroblasts

• Published in: Natural product research 2016-03, Vol.30 (6), p.665-671
• Main Authors: Szoka, Lukasz, Karna, Ewa, Nazaruk, Jolanta, Palka, Jerzy A.
• Format: Article
• Language: English
• Subjects: (Z)-8,9-epoxyheptadeca-1,11,14-triene; Alkenes - pharmacology; Cells, Cultured; Cirsium - chemistry; collagen; Collagen - biosynthesis; Dipeptidases - metabolism; Epoxy Compounds - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibroblasts - drug effects; Fibroblasts - enzymology; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; hypoxia-inducible factor-1α; Insulin-Like Growth Factor I - metabolism; insulin-like growth factor receptor; Integrin beta1 - metabolism; MAP kinases; Molecular Structure; NF-kappa B - metabolism; nuclear factor kappa B; Oils, Volatile - chemistry; Plant Oils - chemistry; Plant Roots - chemistry; Polyenes - pharmacology; prolidase; Receptors, Somatomedin - metabolism
• ISSN: 1478-6419; 1478-6427
• DOI: 10.1080/14786419.2015.1038535

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), β 1 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 β 1 integrin signalling, the effect of EHT on IGF-IR and β 1 integrin receptor expressions were evaluated. Exposure of the cells to EHT contributed to distinct increase in IGF-IR and slight increase in β 1 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.