The comparative release of FGF1 by hypoxia and temperature stress.
The signal peptide-less FGF gene family prototype, FGF1 is released in response to temperature stress in vitro as a latent reducing agent-sensitive homodimer non-covalently complexed with the extravesicular p40 domain of p65 synaptotagmin (Syt)1. Because FGF1 is well recognized as an angiogenesis factor in vivo and angiogenesis is known to be induced by hypoxia, we examined the release of FGF1 and p40 Syt1 under conditions of hypoxia and temperature stress using a chemostatic microcarrier cell culture system. We report that like the pathway used by FGF1 and p40 Syt1 release under temperature stress, hypoxia also induces the release of FGF1 and p40 Syt1 with similar kinetic and pharmacologic properties including the requirement for functional cysteine residues. Lastly, FGF1 and p40 Syt1 release in response to hypoxia and temperature stress is sensitive to lipoxygenase and cyclooxygenase inhibitors suggesting that arachidonic acid metabolism may play an important role in the mechanism of FGF1 release in vitro.
Mouta Carreira
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Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough 04074, USA.
Landriscina
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Bellum
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Prudovsky
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Maciag
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D016475:3T3 Cells; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002135:Calcium-Binding Proteins; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology; D050863:Synaptotagmin I; D050857:Synaptotagmins; D013696:Temperature; D014162:Transfection
D000631:Aminopyridines; D002135:Calcium-Binding Proteins; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009578:Nitrobenzenes; C494310:SYT1 protein, human; D013449:Sulfonamides; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D016220:Fibroblast Growth Factor 1; D015117:5,8,11,14-Eicosatetraynoic Acid; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D050857:Synaptotagmins; D016718:Arachidonic Acid; C045742:amlexanox; D003545:Cysteine