title: alpha(1)-antitrypsin can increase insulin-induced mitogenesis in various fibroblast and epithelial cell lines.
abstract: alpha(1)-Antitrypsin (AT), the archetypal member of the superfamily of serine proteinase inhibitors, inhibits leukocyte elastase activity and thereby can prevent lung damage. Here we show that in fibroblasts from human fetal lung and mouse embryo as well as in certain epithelial cells AT can also enhance the stimulatory effects of insulin on DNA synthesis and cell proliferation. Warming of AT at a moderate (41 degrees C) temperature for a longer time (21 h) or at a higher (65 degrees C) temperature for 30 min before treatment increased its stimulatory effects on both DNA synthesis and activating phosphorylation of p42/p44 mitogen-activated protein kinases. The results suggest that AT may promote regeneration of damaged tissues under pathophysiological conditions which are associated with fever.
authors.affiliation: Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
authors.forename: Q B
authors.initials: QB
authors.lastname: She
authors.forename: J J
authors.initials: JJ
authors.lastname: Mukherjee
authors.forename: K S
authors.initials: KS
authors.lastname: Crilly
authors.forename: Z
authors.initials: Z
authors.lastname: Kiss
mesh_terms: D000469:Alkaline Phosphatase / Q000302:isolation & purification; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis; D004340:Drug Contamination; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006358:Hot Temperature; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000196:embryology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D016895:Culture Media, Serum-Free; D007328:Insulin; D008934:Mitogens; D000515:alpha 1-Antitrypsin; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase