title: Regulation of fibronectin levels by agmatine and spermine in mesangial cells under high-glucose conditions.
abstract: Amines such as agmatine, putrescine, spermidine and spermine have been reported to be involved in a variety of physiological and biochemical phenomena. However, it is not known whether they are also involved in the homeostasis of intracellular fibronectin content via upregulation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and transforming growth factor-beta1 (TGF-beta1). To determine this, we have studied the effect of multiple amines on fibronectin, TGF-beta1, ERK, and PKC levels in mesangial cells under high glucose conditions. All the amines tested (at 0.1-1 mM) affected neither the viability of mesangial cells for 42 h nor LDH release into the medium. Agmatine reduced TGF-beta1 and ERK levels but not PKC at concentrations of 0.1-1 mM. However, levels of fibronectin, TGF-beta1, ERK, and PKC were unaffected by either putrescine or spermidine. A decrease in fibronectin secretion was accompanied by decreases in TGF-beta1 and ERK. Such cumulative results lead us to hypothesize that agmatine reduces high glucose-induced fibronectin secretion via several pathways including ERK-TGF-beta1-fibronectin and spermine, via a decrease in TGF-beta1. Possible roles of enzymes involved in agmatine and polyamine biosynthesis are discussed in relation to secretion of ECM proteins.
authors.affiliation: Department of Biochemistry, College of Science, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Ku, P.O. Box 120-749, Seoul, South Korea.
authors.forename: Geun Taek
authors.initials: GT
authors.lastname: Lee
authors.forename: Young Dong
authors.initials: YD
authors.lastname: Cho
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D005353:Fibronectins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013096:Spermine; D000376:Agmatine; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose