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: Lukasz Szoka, Ewa Karna, Jolanta Nazaruk, Jerzy A Palka
• Journal: Natural product research (Nat Prod Res) Vol. 30 Issue 6 Pg. 665-71 ( 2016) ISSN: 1478-6427 [Electronic] England
• PMID: 25982243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (Z)-8,9-epoxyheptadeca-1,11,14-triene
• Alkenes
• Epoxy Compounds
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Integrin beta1
• NF-kappa B
• Oils, Volatile
• Plant Oils
• Polyenes
• Receptors, Somatomedin
• Insulin-Like Growth Factor I
• Collagen
• Extracellular Signal-Regulated MAP Kinases
• Dipeptidases
• proline dipeptidase

Topics

• Alkenes (pharmacology)
• Cells, Cultured
• Cirsium (chemistry)
• Collagen (biosynthesis)
• Dipeptidases (metabolism)
• Epoxy Compounds (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (drug effects, enzymology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Insulin-Like Growth Factor I (metabolism)
• Integrin beta1 (metabolism)
• Molecular Structure
• NF-kappa B (metabolism)
• Oils, Volatile (chemistry)
• Plant Oils (chemistry)
• Plant Roots (chemistry)
• Polyenes (pharmacology)
• Receptors, Somatomedin (metabolism)