Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic fibroblast growth factor (FGF-2) is a pleiotropic growth factor detected in many different cells and tissues. Normally synthesized at low levels, FGF-2 is elevated in various pathologies, most notably in cancer and injury repair. To investigate the effects of elevated FGF-2, the human full-length cDNA was expressed in transgenic mice under control of a phosphoglycerate kinase promoter. Overexpression of FGF-2 caused a variety of skeletal malformations including shortening and flattening of long bones and moderate macrocephaly. Comparison by Western blot of FGF-2 transgenic mice to nontransgenic littermates showed expression of human FGF-2 protein in all major organs and tissues examined including brain, heart, lung, liver, kidney, spleen, and skeletal muscle; however, different molar ratios of FGF-2 protein isoforms were observed between different organs and tissues. Some tissues preferentially synthesize larger isoforms of FGF-2 while other tissues produce predominantly smaller 18-kDa FGF-2. Translation of the high molecular weight isoforms initiates from unconventional CUG codons and translation of the 18-kDa isoform initiates from an AUG codon in the FGF-2 mRNA. Thus the Western blot data from the FGF-2 transgenic mice suggest that tissue-specific expression of FGF-2 isoforms is regulated translationally.
Mol Biol Cell 1995 Dec
PMID:Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. 859 Aug 11

Basic fibroblast growth factor (FGF-2) is posttranslationally modified by the enzymatic transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD). When sonicated nuclei of adrenal capillary endothelial or SK-Hep1 cells are incubated with [32P]NAD, FGF-2 is rapidly ADP-ribosylated in a dose- and time-dependent fashion. Proteins structurally related to FGF-2 (FGF-6 and -7) are readily modified, suggesting that they share a common substrate motif. Yet, FGF-1, the most structurally homologous member of the FGF family, is a poor substrate. The reaction is also specific; interleukin-1 alpha, transforming growth factor-alpha, nerve growth factor, insulin-like growth factor-I, and granulocyte macrophage-colony stimulating factor are not substrates for ribosylation. Because the ADP ribosylation of FGF-2 is acid resistant but base and hydroxylamine sensitive, the linkage appears to be mediated through arginine. Most importantly, however, we also establish that endogenous FGF-2 is a substrate for ribosylation. As such, an immunoreactive ADP-ribosylated FGF-2 is detected in extracts of SK-Hep1 nuclei when they are incubated with [32P]NAD. Taken together, these findings suggest that the role played by ADP ribosylation in signal transduction, DNA repair, the control of the cell cycle, and cell differentiation may involve its ability to target molecules such as FGF-2.
Mol Endocrinol 1995 Jun
PMID:Adenosine diphosphate ribosylation of fibroblast growth factor-2. 859 22

The present study was undertaken to investigate the regulatory mechanisms of fibroblast growth factor-1 and -2 (FGF-1 and FGF-2) gene expression compared with ciliary neurotropic factor (CNTF) in rat cortical astrocytes. Glial cells represent a source of different trophic factors and cytokines that can influence the survival of multiple cell populations within the central nervous system. We found that the beta-adrenergic receptor agonist (betaAR) isoproterenol produced a significant induction of FGF-2 gene expression and protein in type I astrocytes. On the contrary, the gene expression for FGF-1 and CNTF is markedly reduced after exposure to isoproterenol. The changes produced by the beta AR agonist is mimicked by cyclic AMP analogues (8-bromo-cAMP) or 3-isobutyl-1-methyl-xanthine, a cAMP phosphodiesterase inhibitor, which indicates that intracellular elevation of this second messenger is responsible for these effects. The regulation of neurotrophic factors by isoproterenol is not restricted to cortical astrocytes and may take place through different mechanisms. Inhibition of protein synthesis prevents the decrease in CNTF without affecting the changes in FGF-1 and FGF-2 gene expression. Coincubation of isoproterenol with actinomycin D, an inhibitor of gene transcription, prevents the modification of neurotrophic factor biosynthesis, indicating that transcriptional mechanisms are indeed involved in these regulatory pathways. However, the determination of FGF-2 mRNA half-life suggests that the effect of the betaAR agonist can be in part the result of mRNA stabilization. The mechanisms that we describe can be important in the maintenance of neuronal homeostasis and may be relevant in the development of alternative strategies for the treatment of acute and chronic neurodegenerative disorders
Mol Pharmacol 1996 Apr
PMID:Cyclic AMP-dependent regulation of fibroblast growth factor-2 messenger RNA levels in rat cortical astrocytes: comparison with fibroblast growth factor-1 and ciliary neurotrophic factor. 860 99

In the present report we have studied the effects of acidic and basic molecular forms of the fibroblast growth factor (aFGF, bFGF) on prolactin (PRL) mRNA production and PRL secretion in GH3 cells, a rat pituitary cell line, and their interactions with 17 beta-estradiol (beta E2). To meet this purpose we measured mRNA levels in the cells by both Northern blot and dot blot hybridization analysis, and rPRL immunoreactivity in the culture medium by specific RIA. We observed a marked increase in PRL mRNA levels following 24 h incubation with both basic and acidic FGF. This effect was dose-dependent, with maximal responses ranging between 300 and 600% above the control values. bFGF appeared to be much more potent than aFGF (10-50 times), considering the ED50 of the dose-response curves. Prior incubation with beta E2 (10(-8) M) produced an enhancement in the responses to low doses of bFGF and aFGF, but not to high doses, as revealed by dot-hybridization analysis. Northern blot analysis showed also that both aFGF and bFGF, may have a partially additive effect with beta E2, upon the mature form (1 kb) of rPRL mRNA in GH3 cells. Considering that bFGF is present at high levels in the pituitary, our results suggest that FGF could be a physiological regulatory factor for prolactin production and secretion.
Mol Cell Endocrinol 1995 Oct 30
PMID:Basic and acidic fibroblast growth factor increase prolactin mRNA in a dose-dependent and specific manner in GH3 cells. 867 36

In a cultured hybrid neuronal cell line (BIM) which was produced between human neuroblastoma cells (IMR32) and thymidine auxotrophs (B3T) of rat nerve-like cells (B103), the mRNAs encoding ciliary neurotrophic factor (CNTF) and neurotrophins were detected by the polymerase chain reaction method. The conditioned medium of BIM cells enhanced choline acetyltransferase (ChAT) activity in septal neurons and survival of ciliary ganglion neurons. The mRNA expression of CNTF and neurotrophins in BIM cells was differently regulated by the stimulation with cAMP, FGF and retinoic acid. These data suggest multiple regulation and collaboration of neurotrophic factors.
Biochem Mol Biol Int 1996 Apr
PMID:Expression of mRNA encoding neurotrophic factors and its regulation in a hybrid neuronal cell line. 872 6

We have previously reported that limbic seizures regulate the gene expression of fibroblast growth factor-2 (basic, FGF-2) according to a specific spatio-temporal pattern. In the present paper we have investigated the role of adrenal hormones on seizure-induced elevation of fibroblast growth factor-1 (acidic, FGF-1) and FGF-2 gene expression. Adrenalectomy reduces FGF-2 mRNA expression in specific brain regions, such as frontal cortex, hippocampus and striatum, whereas FGF-1 mRNA levels were decreased only in the frontal cortex. The injection of kainic acid in adrenalectomized rats produced a widespread increase of FGF-2 mRNA with a pattern similar to sham animals as indicated by in situ hybridization. In contrast, although kainate-induced elevation of FGF-1 mRNA in the hippocampus was not influenced by adrenalectomy, its induction in frontal cortex was prevented by this surgery procedure. Taken together, these data indicate that adrenal hormones play a role in the regulation of the gene expression for fibroblast growth factors, but different mechanisms are operative in their induction following seizure activity.
Brain Res Mol Brain Res 1995 Dec 28
PMID:Adrenalectomy reduces FGF-1 and FGF-2 gene expression in specific rat brain regions and differently affects their induction by seizures. 875 Aug 22

Recently we reported that human recombinant acidic fibroblast growth factor (aFGF) is capable of preventing degeneration of nucleus basalis magnocellularis neurons in vivo and inducing growth of astrocytes in vitro. In the present study, the effects of aFGF on the concentration of nerve growth factor (NGF) and its messenger RNA were investigated in the rat cerebral cortex following unilateral cortical infarction. Lesioned animals exhibited a significant increase of NGF in the remaining cortex ipsilateral to the lesion. After combining cortical lesion with intracerebroventricular application of aFGF (12 micrograms/day for 7 days), we observed an 8-fold increase in the NGF concentration and a marked increase in the level of steady state NGF mRNA relative to controls ipsilaterally, and a less pronounced aFGF effect in the contralateral cerebral cortex. These results support the hypothesis that the neurotrophic effects previously shown for aFGF and basic FGF (bFGF) in neurotrophin-sensitive neurons is mediated by inducing increased production of NGF within the injured central nervous system (CNS) of adult animals.
Brain Res Mol Brain Res 1995 Oct
PMID:Acidic FGF induces NGF and its mRNA in the injured neocortex of adult animals. 877 40

Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic effects on brain neurons, glia, and endothelial cells. In the current study, we used Northern blotting, in situ hybridization, and immunohistochemical techniques to examine bFGF expression in brain following focal infarction due to permanent occlusion of the proximal middle cerebral artery in mature Sprague-Dawley rats. We found a four-fold increase in bFGF mRNA in tissue surrounding focal infarcts at 1 day after ischemia. In situ hybridization showed that this increase was found throughout several structures in the ipsilateral hemisphere, including frontoparietal, temporal, and cingulate cortex, as well as in caudoputamen, globus pallidus, septal nuclei, nucleus accumbens, and olfactory tubercle. Increased bFGF mRNA expression was associated with cells having the distinct morphological appearance of astroglia in these structures. Immunohistochemistry showed an increase in the size and number of bFGF-immunoreactive (IR) nuclei in these same structures, as well as a shift from nuclear to nuclear plus cytoplasmic localization of immunoreactivity, beginning at 1 day, and peaking at 3 days after ischemia. Double immunostaining identified bFGF-IR cells as astroglia in these structures. (An exception was the piriform cortex, in which both increased bFGF mRNA levels and increased bFGF-IR was found in neurons at 1 day after ischemia). Overall, the peak of increased bFGF expression preceded the peak in expression of the astroglial marker GFAP within the ipsilateral hemisphere. Increased bFGF expression may play an important role in the glial, neuronal, and vascular changes occurring after focal infarction.
Brain Res Mol Brain Res 1996 Jul
PMID:Increased expression of basic fibroblast growth factor (bFGF) following focal cerebral infarction in the rat. 880 11

We utilized reverse transcription-polymerase chain reaction (RT-PCR) to examine the myocardial mRNA expression of growth factors in mice and children. Total cellular RNA was extracted from these tissues using acidified-phenol guanidinium thiocyanate. Optimal oligonucleotide primer pairs for RT-PCR were selected with the aid of the computer program Oligo 4.0. RT-PCR analysis of total cellular RNA demonstrated the measurable presence of the mRNA for the following growth factors in the myocardium of both mice and children: acidic fibroblast growth factor (aFGF), basic FGF (bFGF), insulin-like growth factor (IGF)-1, IGF-2, platelet-derived growth factor (PDGF)-A chain, PDGF-B chain, transforming growth factor (TGF)beta-1, TGFbeta-2, and TGFbeta-3. The amplified cDNA message for the growth factors and beta-actin migrated as a discrete band at the expected base pair number on agarose gels stained with the intercalating fluorescent dye ethidium bromide. Densitometry of the photographic negatives of these gels permitted the rapid and semiquantitative comparison of these factors. These data demonstrate the feasibility and reproducibility of utilizing RT-PCR for the specific detection and semiquantitation of mRNA expression of myocardial aFGF, bFGF, PDGF-A chain, PDGF-B chain, lGF-1, lGF-2, TGFbeta-1, TGFbeta-2, and TGFbeta-3 in mice and children.
Biochem Mol Med 1996 Feb
PMID:Murine and pediatric myocardial growth factor mRNA expression using reverse transcription-polymerase chain reaction. 881 19

Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis.
Mol Cell Endocrinol 1995 Dec 29
PMID:Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles. 882 88


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