Biomaterial Database

Heparan sulfate proteoglycans control intracellular processing of bFGF in vascular smooth muscle cells. 1998

G V Sperinde, and M A Nugent

Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.

Basic fibroblast growth factor (bFGF) is a potent mitogen for vascular smooth muscle cells (VSMC) and has been implicated in a number of vascular disorders. bFGF interacts with high-affinity receptors and heparan sulfate proteoglycans (HSPG) at the cell surface. HSPG have been demonstrated to enhance bFGF binding to its receptors, yet no known role for HSPG in modulating postbinding events has been identified. In the present study, we analyzed bFGF internalization, intracellular distribution, degradation, and stimulation of DNA synthesis within native and HSPG-deficient VSMC. HSPG-deficient VSMC were generated by treating cells with sodium chlorate to inhibit the sulfation of HSPG. We found that stimulation of DNA synthesis by bFGF in chlorate-treated VSMC was markedly reduced as compared with native cells, even at doses of bFGF where receptor binding was similar in the two conditions. This was not a general lack of mitogenic potential, as the addition of calf serum, or epidermal growth factor, stimulated DNA synthesis to a similar extent in native and chlorate-treated cells. Analysis of the accumulation of internalized bFGF within cytoplasmic and nuclear fractions of native and HSPG-deficient VSMC showed striking differences. At early time points (0-2 h), nearly identical amounts of bFGF were observed in the cytoplasmic fractions under both conditions, yet significant amounts of bFGF were only found in the nuclear fractions of native cells. At later time points (2-48 h), the amount of cytoplasmic bFGF was significantly greater in the native compared to HSPG-deficient cells, and nuclear deposition of bFGF began to reach similar levels under both conditions. Furthermore, the intracellular half-life of bFGF was dramatically prolonged in native compared to HSPG-deficient cells, in part, due to decreased bFGF degradation in native cells. Thus, HSPG appears to accelerate nuclear localization, increase cytoplasmic capacity, and inhibit intracellular degradation of bFGF in VSMC. Modulation of intracellular processing of bFGF by HSPG might control the biological activity of bFGF in VSMC.

UI	MeSH Term	Description	Entries
D007424	Intracellular Fluid	The fluid inside CELLS.	Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011499	Protein Processing, Post-Translational	Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.	Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D002704	Chlorates	Inorganic salts of chloric acid that contain the ClO3- ion.	Chlorate
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia