Regulation of fibronectin levels by agmatine and spermine in mesangial cells under high-glucose conditions.
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.
Lee
Geun Taek
GT
Department of Biochemistry, College of Science, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Ku, P.O. Box 120-749, Seoul, South Korea.
Cho
Young Dong
YD
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
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