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Results for “ELASTIN”

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At least 91 records · Page 5Linked to original sources
PubMed1996

Insulin-like growth factor-I regulates transcription of the elastin gene through a putative retinoblastoma control element. A role for Sp3 acting as a repressor of elastin gene transcription.

Previous studies have demonstrated that insulin-like growth factor-I (IGF-I) increases elastin gene transcription in aortic smooth muscle cells and that this up-regulation is accompanied by a loss of protein binding to the proximal promoter. Sp1 has been identified as one of the factors whose binding is lost, and in the present study we show that Sp3 binding is also abrogated by IGF-I, but in a selected manner. In functional analyses using Drosophila SL-2 cells, Sp1 expression can drive transcription from the elastin proximal promoter, while co-expression of Sp3 results in a repression of Sp1 activity. Footprint and gel shift analyses position the IGF-I responsive sequences to a putative retinoblastoma control element (RCE). Mutation of the putative RCE sequence as assessed by transient transfection of smooth muscle cells results in an increase in reporter activity equal in magnitude to that conferred by IGF-I on the wild type promoter. Together these results support the hypothesis that IGF-I-mediated increase in elastin transcription occurs via a mechanism of derepression involving the abrogation of a repressor that appears to be Sp3 binding to the RCE.

Animals↗
PubMed2005

Biosynthesis of an elastin-mimetic polypeptide with two different chemical functional groups within the repetitive elastin fragment.

A new protein engineering strategy was utilized to synthesize an elastin-mimetic polypeptide. The primary structure represents an elastic motif composed of thirty amino acids with one lysine and one glutamic acid per repeat unit EMM = (VPGVG VPGKG VGPVG VPGVG VPGEG VPGIG). The gene was constructed using a Seamless Cloning method by generating three DNA cassettes which all encoded the EMM repeat unit, but with different flanking restriction recognition sites. The DNA cassettes were assembled to yield a gene that could be directly cloned into the multiple cloning site of pBluescript II SK+. The resulting gene (EMM)(7) with approximately 650 base pairs in length was further cloned into the expression vector pET-28b. Protein biosynthesis in E. coli strain BLR(DE3) resulted in the 21.5 kDa repeating polypeptide His(6)-(EMM)(7) yielding up to 50 mg . L(-1) of cell culture. Secondary structure analysis by far UV circular dichroism revealed a minimum at 197 nm and a shoulder at 218 nm indicative for a random coil with some type II beta-turn conformation content. Lower critical solution temperature (LCST) behavior strongly depends on salt and polypeptide concentration. Importantly, first cross-linking experiments indicate successful hydrogel formation with a surface structure reminiscent to natural elastin as visualized by SEM micrographs.

Base Sequence↗
PubMed1998

Short elastin-like peptides exhibit the same temperature-induced structural transitions as elastin polymers: implications for protein engineering.

Elastin is a major protein component of the vascular wall and is responsible for its unusual elastic properties. Polymers of its repeating VPGVG sequences have been synthesised and shown to exhibit an inverse temperature transition where, as temperature rises, the polymer collapses from an extended chain to a beta-spiral structure with three VPGVG units per turn, each pentamer adopting a type II beta-turn conformation. These studies, however, have not established whether the temperature-driven conformational change is an intrinsic property of the individual pentameric sequences or a global, co-operative effect of many pentamers within the beta-spiral structure. Here, we examine by circular dichroism the behaviour of elastin-like peptides (VPGVG)n, where n varies between 1 and 5. Remarkably, we find that all lengths of peptide undergo an extended left and right arrow beta-turn transition with increasing temperature, suggesting that the induction of the beta-spiral occurs at the level of single pentameric units. The origin of this effect is a positive DeltaS term for the transition. At 35 degreesC, the average transition midpoint temperature, the value of TDeltaS is about 15 kcal mol-1. With larger oligomers (n=3), there is only a modest rise in DeltaS, suggesting that the dominant entropic effect resides within the monomer and that interactions between these units make only a small contribution to the energetics of the transition. Charges at the termini, and residue replacements or additions, regulate the transitions for the short peptides in a manner similar to that observed for the longer polymers. The behaviour of the same peptides in trifluoroethanol and SDS solutions is consistent with formation of the beta-turn being driven by interactions between non-polar groups. The significance of this behaviour for the rational design of temperature-induced responses in proteins is discussed.

Amino Acid Sequence↗
PubMed1997

Effect of lithium on superoxide production and intracellular free calcium mobilization in elastin peptide (kappa-elastin) and FMLP stimulated human PMNS. Effect of age.

The effect of lithium pretreatment on superoxide anion production and intracellular free calcium levels was investigated in polymorphonuclear leukocytes (PMN) from middle-aged and old individuals after stimulation by elastin peptides or FMLP. K-elastin (KE) significantly stimulated the production of superoxide anion by PMNs from middle-aged subjects, while this stimulation decreased with age and was absent in PMNs of elderly arteriosclerotic patients. Li pretreatment slightly increased this stimulating effect of KE in PMNs from middle-aged subjects and elderly arteriosclerotic patients, while slightly decreased in healthy elderly subjects. Moreover, Li was able to increase superoxide anion production even in the absence of KE, but this effect decreased also in PMNs of healthy and arteriosclerotic elderly patients. FMLP significantly increased superoxide anion production in all age-groups, but this effect was further amplified by Li only in PMNs of middle-aged subjects. In aged individuals Li pretreatment slightly decreased the effect of FMLP and had no effect in arteriosclerotic patients. Ca-mobilization induced by KE was inhibited by Li pretreatement in each age group. This inhibition by Li was much weaker in FMLP-stimulated PMNs. Li pretreatment did however modify the shape of the Ca-transient curves in FMLP stimulated leukocytes suggesting a qualitative modification of ion channel regulation. No such shape change of Ca-transient curves was observed after KE stimulation of Li pretreated PMNs. It appears that the regulation of these two receptors is differently affected by Li treatment.

Adult↗
PubMed1988

Increased elastin production by progeria skin fibroblasts is controlled by the steady-state levels of elastin mRNA.

Hutchinson-Gilford progeria is a unique, rare disease with markedly accelerated aging. The average lifespan of affected individuals is 12 years. Although the biochemical basis of the syndrome is unknown, its influence appears to be primarily upon mesodermal tissues. Characteristics such as the altered appearance of the skin and the extensive and fatal involvement of the cardiovascular system led us to study elastin production in cultured skin fibroblasts from three progeroid individuals. We found tropoelastin production by progeroid cells was elevated six- to nine-fold at the protein and mRNA levels, while relative collagen synthesis was similar to control strains. There was little difference between progeroid and normal cells in expression of total protein or in total cellular mRNA content. Western blot analysis of tropoelastin from progeroid fibroblasts confirmed increased production of elastin but revealed no gross changes in the molecular mass. The significant increase in tropoelastin expression lends support to the concept that progeria results from a mesenchymal dysplasia, and offers a possible biochemical marker for the phenotype.

Adolescent↗
PubMed1976

Effect of hydrophobic elastin ligands on the stress-strain properties of elastin fibers.

Alkyl sodium sulfates as well as sodium oleate previously shown to bind to insoluble elastin markedly decrease the tensile strength of fibers of ligament elastin. This effect correlates with the increasing number of carbon atoms in the detergent molecules. These data support previously proposed models which emphasize the importance of hydrophobic bonding to the elastic properties of this connective tissue protein.

Animals↗
PubMed1987

Immunology of elastin: study of anti-elastin peptide antibodies by DOT immunobinding assay.

In order to further investigate the role of the immune system in the arteriosclerotic process, we investigated the anti-elastin peptide antibodies (AEAb) of the IgG and IgM types by DOT immunobinding assay in the sera of patients suffering from various arteriosclerotic diseases. In total 232 control and pathological sera were studied. In obliterative arteriosclerosis of the legs 90%, ischemic heart disease 67% and hypertension 60% of sera were positive for AEAb of the IgG type independent of age. In the case of diabetes mellitus, however, the duration of the disease was determinant. In rheumatoid arthritis, the results were negative. No clear-cut positivity could be demonstrated in stroke patients either. These results indicate that AEAb can be detected in some diseases and DOT appears to be an appropriate method for the AEAb screening in various diseases.

Adult↗
PubMed2000

Decreased elastin deposition and high proliferation of fibroblasts from Costello syndrome are related to functional deficiency in the 67-kD elastin-binding protein.

Costello syndrome is characterized by mental retardation, loose skin, coarse face, skeletal deformations, cardiomyopathy, and predisposition to numerous malignancies. The genetic origin of Costello syndrome has not yet been defined. Using immunohistochemistry and metabolic labeling with [3H]-valine, we have established that cultured skin fibroblasts obtained from patients with Costello syndrome did not assemble elastic fibers, despite an adequate synthesis of tropoelastin and normal deposition of the microfibrillar scaffold. We found that impaired production of elastic fibers by these fibroblasts is associated with a functional deficiency of the 67-kD elastin-binding protein (EBP), which is normally required to chaperone tropoelastin through the secretory pathways and to its extracellular assembly. Metabolic pulse labeling of the 67-kD EBP with radioactive serine and further chase of this tracer indicated that both normal fibroblasts and fibroblasts from patients with Costello syndrome initially synthesized comparable amounts of this protein; however, the fibroblasts from Costello syndrome patients quickly lost it into the conditioned media. Because the normal association between EBP and tropoelastin can be disrupted on contact with galactosugar-bearing moieties, and the fibroblasts from patients with Costello syndrome revealed an unusual accumulation of chondroitin sulfate-bearing proteoglycans (CD44 and biglycan), we postulate that a chondroitin sulfate may be responsible for shedding EBP from Costello cells and in turn for their impaired elastogenesis. This was further supported by the fact that exposure to chondroitinase ABC, an enzyme capable of chondroitin sulfate degradation, restored normal production of elastic fibers by fibroblasts from patients with Costello syndrome. We also present evidence that loss of EBP from fibroblasts of Costello syndrome patients is associated with an unusually high rate of cellular proliferation.

Abnormalities, Multiple↗
PubMed1989

Structure of the bovine elastin gene and S1 nuclease analysis of alternative splicing of elastin mRNA in the bovine nuchal ligament.

Genomic clones encompassing all the translated sequences, the 3' untranslated sequence, and 1 kb flanking the ATG translation initiation codon of bovine tropoelastin have been obtained and characterized by restriction enzyme analysis and extensive DNA sequencing. These analyses demonstrated that functionally distinct hydrophobic and cross-linking domains of the protein are segregated into separate exons throughout the gene. The putative promoter region lacks a TATA box, has an extremely high G+C content, and contains several SP1 binding sites. Comprehensive S1 analyses using probes covering the entire mRNA and RNA isolated from the nuchal ligament of bovine fetuses of different ages, neonate calves, and adult cows demonstrated that while only a single exon is alternatively spliced at high frequency, many exons are alternatively spliced at limited, variable frequencies. The results also suggest that such limited splicing is increased in the adult tissue relative to fetal and neonate tissues.

Amino Acid Sequence↗