S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro.
We have previously characterized the release of the signal peptide sequence-less fibroblast growth factor (FGF) prototype, FGF-1, in vitro as a stress-induced pathway in which FGF-1 is released as a latent homodimer with the p40 extravesicular domain of p65 synaptotagmin (Syn)-1. To determine the biologic relevance of the FGF-1 release pathway in vivo, we sought to resolve and characterize from ovine brain a purified fraction that contained both FGF-1 and p40 Syn-1 and report that the brain-derived FGF-1:p40 Syn-1 aggregate is associated with the calcium-binding protein, S100A13. Since S100A13 binds the anti-inflammatory compound amlexanox and FGF-1 is involved in inflammation, we examined the effects of amlexanox on the release of FGF-1 and p40 Syn-1 in response to stress in vitro. We report that while amlexanox was able to repress the heat shock-induced release of FGF-1 and p40 Syn-1 in a concentration-dependent manner, it had no effect on the constitutive release of p40 Syn-1 from p40 Syn-1 NIH 3T3 cell transfectants. These data suggest the following: (i) FGF-1 is associated with Syn-1 and S100A13 in vivo; (ii) S100A13 may be involved in the regulation of FGF-1 and p40 Syn-1 release in response to temperature stress in vitro; and (iii) the FGF-1 release pathway may be accessible to pharmacologic regulation.
Mouta Carreira
C
C
Center for Molecular Medicine, Maine Medical Center Research Institute, South Portland, Maine 04106, USA.
LaVallee
T M
TM
Tarantini
F
F
Jackson
A
A
Lathrop
J T
JT
Hampton
B
B
Burgess
W H
WH
Maciag
T
T
D000287:Administration, Topical; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000378:metabolism*; D018869:Heat-Shock Response; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011489:Protein Denaturation; D009418:S100 Proteins / Q000378:metabolism*; D012756:Sheep; D050863:Synaptotagmin I; D050857:Synaptotagmins
D000631:Aminopyridines; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D006634:Histamine H1 Antagonists; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009418:S100 Proteins; D050863:Synaptotagmin I; D050857:Synaptotagmins; D005346:Fibroblast Growth Factors; C045742:amlexanox