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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic fibroblast growth factor (bFGF or FGF-2) is produced by nearly all melanomas in vitro and in vivo but not by normal melanocytes, which require exogenous bFGF for growth. In this study, we transduced normal human melanocytes to overexpress two forms of bFGF: (bFGF-Long and bFGF-Short) using replication-deficient adenovirus 5 vectors. bFGF-Long induced the 17.8, 22.5, 23.1 and 24.2 kDa forms of bFGF, whereas bFGF-Short induced only the 17.8 kDa mature form. Growth of cultured melanocytes transduced with either vector was similar to that of nevus and melanoma cells and was independent of exogenous bFGF and of insulin/insulin-like growth factor 1, and cyclic AMP enhancers, requiring only phorbol ester as an exogenous mitogen. Like primary melanoma cells, transduced normal melanocytes grew anchorage independently in soft agar. When injected into the dermis of human skin grafted to mice, bFGF-transduced melanocytes proliferated for at least 20 days, whereas cells from control cultures showed poor survival and no proliferation. These results demonstrate that bFGF upregulation is a critical component in melanoma progression.
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PMID:Basic fibroblast growth factor induces a transformed phenotype in normal human melanocytes. 1059 49

A fibrino(geno)lytic nonhemorrhagic metalloprotease (neuwiedase) was purified from Bothrops neuwiedi snake venom by a single chromatographic step procedure on a CM-Sepharose column. Neuwiedase represented 4.5% (w/w) of the crude desiccated venom, with an approximate Mr of 20,000 and pI 5.9. As regards the amino acid composition, neuwiedase showed similarities with other metalloproteases, with high proportions of Asx, Glx, Leu, and Ser. Atomic absorption spectroscopy showed that one mole of Zn2+ and one mole of Ca2+ were present per mole of protein. The cDNA encoding neuwiedase was isolated by RT-PCR from venom gland RNA, using oligonucleotides based on the partially determined amino-acid sequences of this metalloprotease. The full sequence contained approximately 594 bp, which codified the 198 amino acid residues with an estimated molecular weight of 22,375. Comparison of the nucleotide and amino acid sequences of neuwiedase with those of other snake venom metalloproteases showed a high level of sequential similarity. Neuwiedase has two highly conserved characteristics sequences H142E143XXH146XXG149XXH152 and C164I165M166. The three-dimensional structure of neuwiedase was modeled based on the crystal structure of Crotalus adamanteus Adamalysin II. This model revealed that the zinc binding site region showed a high structural similarity with other metalloproteases. The proteolyitc specificity, using the Bbeta-chain of oxidized insulin as substrate, was shown to be directed to the Ala14-Leu15 and Tyr16-Leu17 peptide bonds which were preferentially hydrolyzed. Neuwiedase is a Aalpha,Bbeta fibrinogenase. Its activity upon the Aalpha chain of fibrinogen was detected within 15 min of incubation. The optimal temperature and pH for the degradation of both Aalpha and Bbeta chains were 37 degrees C and 7.4-8.0, respectively. This activity was inhibited by EDTA and 1,10-phenantroline. Neuwiedase also showed proteolytic activity upon fibrin and some components of the extracellular matrix. However, it did not show TAME esterase activity and was not able to inhibit platelet aggregation.
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PMID:Structural and functional characterization of neuwiedase, a nonhemorrhagic fibrin(ogen)olytic metalloprotease from Bothrops neuwiedi snake venom. 1103 8

To investigate the cooperativity of insulin's structure, a cavity-forming substitution was introduced within the hydrophobic core of an engineered monomer. The substitution, Ile(A2)-->Ala in the A1-A8 alpha-helix, does not impair disulfide pairing between chains. In accord with past studies of cavity-forming mutations in globular proteins, a decrement was observed in thermodynamic stability (DeltaDeltaG(u) 0.4-1.2 kcal/mole). Unexpectedly, CD studies indicate an attenuated alpha-helix content, which is assigned by NMR spectroscopy to selective destabilization of the A1-A8 segment. The analog's solution structure is otherwise similar to that of native insulin, including the B chain's supersecondary structure and a major portion of the hydrophobic core. Our results show that (1) a cavity-forming mutation in a globular protein can lead to segmental unfolding, (2) tertiary packing of Ile(A2), a residue of low helical propensity, stabilizes the A1-A8 alpha-helix, and (3) folding of this segment is not required for native disulfide pairing or overall structure. We discuss these results in relation to a hierarchical pathway of protein folding and misfolding. The Ala(A2) analog's low biological activity (0.5% relative to the parent monomer) highlights the importance of the A1-A8 alpha-helix in receptor recognition.
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PMID:A cavity-forming mutation in insulin induces segmental unfolding of a surrounding alpha-helix. 1174 27

The main goal of this study was to prepare molecularly imprinted polymers (MIPs) with glucose recognition sites and to evaluate their glucose-binding properties for potential applications in glucose sensing and self-regulating insulin delivery devices. To mimic glucose-binding sites of natural proteins, monomers possessing functional groups similar to amino acids were used. Vinyl acetic acid (VAA), acrylamide (AAm), 4-pentenoic acid (PA), and allyl benzene (AB) were copolymerized with a cross-linking agent (N,N'-methylenebisacrylamide, BIS) in the presence of glucose as a template. The binding affinity of glucose to MIPs was examined by using an equilibrium dialysis technique. The dissociation constants of the MIPs were determined by Scatchard analysis. MIPs showed glucose-binding affinity, while polymers synthesized in the absence of glucose template did not show a glucose-binding property. MIPs composed of VAA, AAm, PA, and AB at optimized mole ratios of monomers and cross-linker showed the highest glucose-binding affinity, KD = 1.66 mM, which is comparable to that of a well-known glucose binding protein, concanavalin A (KD = 1.84 mM). The affinity between monomer and glucose was in the order VAA > AAm > AB > PA.
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PMID:Glucose binding to molecularly imprinted polymers. 1218 49

Palladium(II) ions anchored to side chains of histidine and methionine residues in peptides and proteins in weakly acidic aqueous solutions promote hydrolytic cleavage of proximate amide bonds in the backbone. In this study, we determine how attachment of Pd(II) ions to histidine and methionine anchors and also to the terminal amino group in six natural peptides (chains A and B of insulin, segment 11-14 of angiotensinogen, pentagastrin, angiotensin II, and segment 3-8 of angiotensin II) and two proteins (ubiquitin and cytochrome c) affects regioselectivity and rate of backbone cleavage. These Pd(II)-promoted reactions follow a clear pattern of regioselectivity, directed by the anchoring side chains. When the Pd(II) reagent is nonspecifically anchored to the terminal amino group, the ligating site that is present in almost all proteins, the cleavage is fortunately absent. When the reagent is anchored to a residue in positions 1, 2, or 3, cleavage is absent, because the terminal amino group and deprotonated amide nitrogen atom(s) interposed between it and the anchor "lock" the Pd(II) ion in hydrolytically inactive chelate complexes. When the reagent is anchored to residues in positions beyond 3, the second amide bond upstream from the anchor is regioselectively cleaved in all cases when the anchor was "isolated," that is, flanked by noncoordinating side chains. Segment 3-8 of angiotensin II undergoes additional cleavage, which we explain by determining the rate constants for the cleavage, identifying the rate-limiting displacement of ethylenediamine ligand from the Pd(II) ion, and detecting several intermediates. Experiments with cytochrome c demonstrate that the number of cleavage sites can be controlled by adjusting the mole ratio of the Pd(II) reagent to the substrate. Our inorganic peptidases are useful for biochemical applications because their regioselectivity and reactivity set them apart from proteolytic enzymes and organic chemical reagents.
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PMID:Interplay of terminal amino group and coordinating side chains in directing regioselective cleavage of natural peptides and proteins with palladium(II) complexes. 1249 44

Thermoresponsive hydrogels were synthesized by radiation copolymerization of ethylene glycol vinyl ether (1) and butyl vinyl ether (2) in the presence of cross-linking agent diethylene glycol divinyl ether. The comonomer ratio (monomer 1/monomer 2) and the cross-linker concentration were kept constant at 60:40 (mole percentage in the monomeric mixture) and 4% (mole basis), respectively. The hydrogels showed a volume-phase transition in the temperature range 10-25 degrees C and their swelling behaviour was reversible. The gels were modified by a cell adhesion factor, the RGD sequence of fibronectin, and a cell growth factor, insulin. However, they lost their thermoresponsive character after modification. The use of the gels in cell culture was investigated without using a proteolytic enzyme or serum. Cell culture studies realized by human skin fibroblasts (HS An1) showed that the cells can attach and proliferate on the surface of a thermoresponsive polymer. 80% of the cultured cells were readily detached from the polymer surface by lowering the incubation temperature from 37 degrees C to 10 degrees C for 30 min. In the studies carried out with RGD or insulin-modified hydrogels in serum-free cultures, higher values of cell proliferation (9 x 10(5) cells/ml) were obtained on the insulin-modified hydrogels, whereas higher values of cell attachment were obtained on the RGD-immobilized surfaces.
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PMID:Uses of thermoresponsive and RGD/insulin-modified poly(vinyl ether)-based hydrogels in cell cultures. 1271 94

Nevi, or moles, are localized nevocytic tumors. The American Cancer Society's "ABCD" rules are useful for differentiating a benign nevus from malignant melanoma. While acanthosis nigricans may signal an underlying malignancy (e.g., gastrointestinal tumor), it more often is associated with insulin resistance (type 2 diabetes, polycystic ovary syndrome) or obesity. Melasma is a facial hyperpigmentation resulting from the stimulation of melanocytes by endogenous or exogenous estrogen. Treatments for melasma include bleaching agents, laser therapy, and a new medication that combines hydroquinone, tretinoin, and fluocinolone acetonide. Lesions that develop on the shins of patients with diabetic dermopathy often resolve spontaneously; no treatment is effective or recommended. Tinea versicolor responds to treatment with selenium sulfide shampoo and topical or oral antifungal agents. Postinflammatory hyperpigmentation or hypopigmentation can occur in persons of any age after trauma, skin irritation, or dermatoses.
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PMID:Common hyperpigmentation disorders in adults: Part II. Melanoma, seborrheic keratoses, acanthosis nigricans, melasma, diabetic dermopathy, tinea versicolor, and postinflammatory hyperpigmentation. 1465 5

The complexes of chromium(III) ion formed by salicylic acid, SA(H(2)L), and its derivatives (H(2)L): 5-nitrosalicylic acid (5-NSA), 5-sulphosalicylic acid (5-SSA) were investigated by means of potentiometry and spectroscopy, at 25 degrees C and in ionic strength of 0.1 M KNO(3) and 0.1 M KCl, respectively. Over the acidic pH range, the coordination of Cr(III) ion to SA and its derivatives in 1 : 1 mole ratio occurs, CrL(+) type complex is formed. In the excess of ligand, the coordination of the second ligand molecule is somewhat hindered; as a result CrL(HL) type complex occurs. Their existences were verified and their formation constants were determined. At near neutral pH, CrL(OH) and CrL(HL)(OH)(-) type hydroxo complexes formed by hydrolytic equilibria and their formation constants were also defined. The stabilities of Cr(III) complexes of SA and its derivatives decrease in the following order: SA>5-SSA>5-NSA. The formation constants of Cr(III) complexes of SA and its derivatives are in comparable ranges with the corresponding complexes of the 2,x-dihydroxybenzoic acid (2,x-DHBA) of Cr(III) ion. The stabilities of SA complexes for V(IV), Cr(III) and Fe(III) ions that have similar ionic radii, increase in the order VOL<CrL(+)<FeL(+). It is worthwhile noting that the binding ability of Cr(III) to salicylate ion is four orders of magnitude higher than to transferin, which is a blood serum protein and is associated with insulin action.
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PMID:Equilibrium studies on chromium(III) complexes of salicylic acid and salicylic acid derivatives in aqueous solution. 1551 46

Endocrine cell distribution within the islets of Langerhans may vary both between species and under different energetically demanding conditions such as cold acclimation. The naked mole-rat, Heterocephalus glaber, lacking an effective insulatory pelage, is effectively a poikilotherm, yet it shows a typical mammalian cold-acclimation response by substantially increasing food intake to meet higher energy requirements when housed at lower temperatures. The endocrine component of the pancreas of thermoneutral and cold-acclimated naked mole-rats was thus characterized using immunocytochemistry and ultrastructural analyses. Four distinct endocrine cells were identified: alpha (glucagon-producing), beta (insulin-producing), delta (somatostatin-producing), and PP (pancreatic polypeptide-producing) cells. Distribution of these cells differed from that of other rodents, in that beta cells formed the mantle while alpha cells formed the core of the islets. This distribution may contribute to the observed insulin insensitivity of this species, as indicated in abnormal responses to glucose tolerance tests. Insulin-producing cells, however, were more numerous than glucagon-producing cells. This ratio was unchanged with cold acclimation. Immunoreactivity of alpha and beta cells was more intense in cold-acclimated than in thermoneutral animals, possibly indicative of a change in hormonal production in animals housed at a lower temperature.
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PMID:The pancreas of the naked mole-rat (Heterocephalus glaber): an ultrastructural and immunocytochemical study of the endocrine component of thermoneutral and cold acclimated animals. 1556 Aug 67

The determination of the fluorophore to the protein molar ratio has been studied using fluorescence spectroscopy. The tyrosine fluorescence is measured from insulin (Ins) solutions at wavelengths lambda(ex)/lambda(em) = 276/300 nm and from fluorescein isothiocyanate (FITC) solutions at lambda(em)/lambda(em) = 494/518 nm. Series of solutions prepared from insulin and FITC are tested for conjugation, recording their fluorimetric intensities. Fluorimetric titrations with different formal concentrations are followed either by intrinsic and extrinsic emission intensities at lambda(ex)/lambda(em) = 276 or 494/518 nm and by their typical emission spectra at pH 9.0. All results denoted a binding ratio of 3 moles of FITC/mole of Ins.
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PMID:Binding of fluorescein isothiocyanate to insulin: a fluorimetric labeling study. 1561 46


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