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en] Chloro-4-phenyl thiomethylene bisphosphonate (tiludronate) is a new drug which can be used as an inhibitor of bone resorption. As it remains in bone for a long time, and as mineralisation defects have only been seen at doses much higher than those required to decrease osteoclastic activity, it could be given at high doses over a short period of time. Eighteen patients with Pagets disease of bone were randomly allocated to three therapeutic groups receiving respectively 600, 800, and 1200 mg/day tiludronate for five days. Serum alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio were quickly and drastically reduced in all three groups. A significant reduction of serum alkaline phosphatases and the hydroxyproline/creatinine ratio was still present six months after the five day therapeutic course, reflecting a sustained activity of tiludronate even after stopping treatment. Dose dependent short and long term reductions of bone turnover rate were observed. Biochemical ...
We report data from three patients with severe Pagets disease of bone who were treated with mithramycin.. Mithramycin infusion resulted in a fall in plasma calcium, phosphate, alkaline phosphatase, and urinary hydroxyproline excretion. There was an improvement in calcium and phosphorus balance in two of the three subjects studied. A pronounced or complete relief of bone pain occurred in all three.. We suggest that mithramycin exerts its beneficial effect in Pagets disease of bone by stimulating parathyroid hormone release. The parathyroid hormone released has a predominantly anabolic action on bone since its catabolic action is blocked by mithramycin, which inhibits bone resorption.. ...
Saline extracts of potato tubers contain a potent hemagglutininin that is not inhibited by monosaccharides. Carbohydrate inhibition studies have shown that the lectin has an extended binding site that can accommodate up to four carbohydrate units. The lectin binds oligosaccharides containing β(1,4)-linked GlcNAc. The tetrasaccharide is approximately 20 times more potent an inhibitor than the disaccharide 1 . STA also reacts with poly N-acetyllactosamine structures from N-linked oligosaccharides, albeit rather weakly 2 . Nevertheless, it is useful for histochemical staining of these structures 3 . Many lectins do not react with sulfated sugars, however, STA does bind to chitin sulfates and keratan sulfates 4 . Purified STA is one of the most highly glycosylated lectins, composed of approximately 50% carbohydrate by weight. The heavily-glycosylated portion is a hydroxyproline-containing sequence homologous to the cell wall extensions, while the carbohydrate-binding region is rich in cysteine and ...
Young (3 mo old) and old (18-24 mo old) wild-type (WT) and SPARC-null mice were studied. LV collagen content was measured histologically by collagen volume fraction, collagen composition was measured by hydroxyproline assay as soluble collagen (1 M NaCl extractable) versus insoluble collagen (mature cross-linked), and collagen morphological structure was examined by scanning electron microscopy ...
Description: The chemical reactions and pathways involving 4-hydroxyproline, C5H9NO3, a derivative of the amino acid proline. The presence of hydroxyproline is essential to produce stable triple helical tropocollagen, hence the problems caused by ascorbate deficiency in scurvy. This unusual amino acid is also present in considerable amounts in the major glycoprotein of primary plant cell walls.. ...
Yup, Ive been expressing bewilderment for months now as to why STURPs Ray Rogers (left) thought there was hydroxyproline in human blood. He cited the presence of hydroxyproline as crucial evidence against the Shroud blood ever having been heated, using that to dismiss any idea that the body image was a thermal imprint (scorch) -…
MIT and Harvard University chemists have discovered the structure of an unusual bacterial enzyme that can break down an amino acid found in collagen, which is the most abundant protein in the human body. The enzyme, known as hydroxy-L-proline dehydratase (HypD), has been found in a few hundred species of bacteria that live in the human gut, including Clostridioides difficile. The enzyme performs a novel chemical reaction that dismantles hydroxy-L-proline, the molecule that gives collagen its tough, triple-helix structure. Now that researchers know the structure of the enzyme, they can try to develop drugs that inhibit it. Such a drug could be useful in treating C. difficile infections, which are resistant to many existing antibiotics. "This is very exciting because this enzyme doesnt exist in humans, so it could be a potential target," says Catherine Drennan, PhD, an MIT Professor of Chemistry and Biology and a Howard Hughes Medical Institute Investigator. "If you could potentially inhibit that ...
The most important problem relating to safety and scientific feasibility of regular intake of MCPs is elevated from the nicely founded fact that the induction of collagen synthesis, generally assessed through the greater hydroxyproline concentrations, is usually connected to oxidative worry [28-thirty]. Also, MCPs of various origin are already proven to activate innate immune reaction of macrophages and neutrophils via Toll-like receptor 4, which leads to NADPH-oxidase (NOX4) activation and reactive oxygen species overproduction [31, 32 ...
[65 Pages Report] Check for Discount on TRANS METHYL O-BENZYL-L-4-HYDROXYPROLINE Global Market and Forecast Research report by ChemReport. DescriptionWe provide independent and unbiased information on manufacturers, prices, production...
As a clarification of the above, molecular oxygen, as I understand it, is necessary for the post-transcriptional hydroxylation of proline to hydroxyproline - ie the oxygen in the hydroxyproline does not come from water, but is added from an O2 molecule by an oxygenase enzyme.. The hydroxyprolines are critical for collagen strength. Thus in the complete absence of O2, animals bodies simply would not be able to hold together beyond a certain size (hence my first question about whether or not the small size gets around the problem).. The level of O2 needed is actually much lower than current atmospheric O2 in aerobic environments, and may be low enough that it could be found even in environments that would be considered to be hypoxic. But the post seemed to suggest that these animals lived in a completely anoxic environment - there is no O2 at all? If which case, how do these animals synthesize collagen?. ...
Rabbit polyclonal Hydroxyproline antibody validated for WB, IHC. Referenced in 3 publications and 3 independent reviews. Immunogen corresponding to synthetic…
TABLE-US-00001 NAME OF RAW MATERIAL WEIGHT % (MANUFACTURER) INCI 1 2 3 4 5 6 7 8 9 10 Pseudoceramides Pseudoceramide 176 N-(1-dodecanoyl)-4- 0.1 0.2 0.1 hydroxy-L-proline 1- hexadecyl ester Pseudoceramide 391 N-(1-hexadecanoyl)-4- 0.2 0.1 0.1 0.1 0.2 0.5 hydroxy-L-proline 1- hexadecyl ester Ceramide PC104 (Pacific hydroxypropyl- 0.1 Corporation) bispalmitamide MEA Ceramide SL (Sino Lion) hydroxyethyl-palmityl- 0.1 oxyhydroxypropyl- palmitamide Aqua-Ceramide (Kao) cetyloxypropyl-glyceryl- 0.1 0.1 methoxypropyl- myristamide Ceramides Ceramide 2 (Sederma) ceramide 2 0.1 Ceramide III (Cosmoferm) ceramide 3 0.1 Bisabolol (Alpha-)Bisabolol, natural bisabolol 0.2 0.3 0.2 0.5 0.1 (Symrise) Dragosantol (Symrise) bisabolol 0.3 0.4 0.2 0.3 0.3 Fatty acids Linoleic Acid linoleic acid 0.1 0.2 Palmitic Acid palmitic acid 0.1 0.1 0.2 Stearic Acid stearic acid 0.1 Sterols Cholesterol (Croda) cholesterol 0.1 0.5 Tamasterol (Tama Biochemicals) phytosterol 0.2 Other ingredients Abil 350 (Degussa- dimethicone 0.5 ...
Polyribosomes containing nascent [3H]proline-labeled collagen chains were isolated from chick embryo fibroblasts in culture. These nascent chains were nearly completely hydroxylated, as indicated by the presence of [3H]hydroxyproline and high hydroxyproline/proline ratios. The polyribosomes were suspended in D2O at 15 degrees and the infrared spectrum was determined using a reference cell containing collagen-depleted polyribosomes in D2O, matched to equal RNA content. The amide I and amide II bands were observed. When the polyribosomes were heated in D2O at 44 degrees in the infrared cells, the N--D amide II absorbance at 1480 cm-1 increased markedly, indicating that H leads to D exchange had occurred. Collagen-depleted polyribosomes showed no such changes in absorbance at 1450-1480 cm-1 upon heating. Polyribosomes recovered from the infrared cells after treatment at 44 degrees and cooling still contained collagen, as indicated by their [3H]hydroxyproline content. These data indicate that ...
Hello Kapil,. Thanks for your interesting questions.. Sorry for the delayed replay. I was swamped in my work for a while, needless to explain the pressure.. Answer to your 1st question: As we all know, speed vac or centrifugal evaporator works by reducing the pressure under vacuum so does the boiling point of a given solvent. The centrifugal force generated during this process will evaporate the solvent from top, thus it prevent loss or solute by solvent bumping (in other words, by violent boiling). During centrifugal evaporation of HCl from our sample, we all assume that there will be a small loss of hydroxy proline (HYP) but this will be a similar error if we treat all our samples in the same way. It is known that the loss of HYP on drying is ≤ 0.1% at 110 C and I am sure centrifugal evaporator with no heat (assuming we are not using heating option in the instrument) will not reach this temp.. In summary, you have to dry the HCl in the absence of heat in centrifugal evaporator. If you are ...
The intrinsic capacity of tendons to heal in response to injury has recently been demonstrated by many investigators. Electrical stimulation is often assumed to augment regeneration of various tissues. Using newly developed methods of whole-tendon culture, the authors examined the effect of direct-current electricity on healing in vitro. Deep flexor tendons of rabbits were excised, transected, repaired, and grown in an acellular culture medium for seven, 14, 21, or 42 days. Tendons through which a continuous 7-microAmp current was passed at the repair site were compared with nonstimulated controls. The incorporation of (14C)proline and its conversion to (14C)hydroxyproline was measured at seven days. The mean (14C)proline and (14C)hydroxyproline activities were 91% and 255% greater, respectively, in the stimulated group. The activity was also higher in the stimulated group, by 42 days. Histologic sections showed that intrinsic tenoblastic repair may be enhanced with electrical stimulation in ...
The collagen triple helix is stabilized by interchain hydrogen bonds. The sequence of the protein in the helical region consists of multiple repeats of the form -Gly-X-Y-, where X is often proline and Y is often a modified proline called 4-hydroxyproline. The glycine residues are located along the central axis of the triple helix, where tight packing of the protein strands can accommodate no other residue. For each -Gly-X-Y- triplet, one hydrogen bond forms between the amide hydrogen atom of glycine in one chain and the carbonyl oxygen atom of residue X in an adjacent chain. Hydrogen bonds involving the hydroxyl group of hydroxyproline may also stabilize the collagen triple helix. Unlike the more common α helix, the collagen helix has no intrachain hydrogen bonds ...
Background. Bone mineral density (BMD) is used to follow gain or loss of bone mass but cannot detect changes within a short period of time. Biochemical markers of bone turnover may be of value for prediction of individual bone loss.. Methods. We studied the relation between common inexpensive markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin (OC), urinary hydroxyproline (OHPr), and calcium (Ca)), BMD, age, and menopause in a combined cross-sectional and longitudinal design comprising 429 pre- and postmenopausal randomly selected women aged 21-79 years (mean 50 years). A follow-up was initiated after 5 years (including 192 of these women), which focused on changes in bone mass and the ability of these four common markers of bone turnover (sampled at baseline) to predict future bone loss.. Results. A marked increase was observed for all markers at the beginning of menopause. During the postmenopausal period ALP and Ca decreased to near premenopausal levels, while OC and OHPr ...
Proline has been grafted onto silica supports in a single step by reacting trans-4-hydroxy-l-proline with chloropropyl tethers, without the use of protecting groups for the proline amine and carboxylic acid functional groups. The resulting catalysts have been characterised to show that grafting is through re Catalysis on Chiral Surfaces: From Fundamental Aspects to Application
Anti-fibrosis treatment with prizaquantel reduced areas of liver Sirius Red staining and liver hydroxyproline contents of mice 8 weeks post infection with Schis
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Soluble Collagen refers to the big, natural collagen molecules mostly extracted from fish or bovine skin. Spotting collagen on the ingredient...
Prolyl 4-hydroxylase (EC 1.14.11.2) catalyzes the formation of4-hydroxyproline in collagens by the hydroxylation of proline residues inX-Pro-Gly sequences. The reaction requires Fe2+, 2-oxoglutarate, O2, andascorbate and involves an oxidative decarboxylation of 2-oxoglutarate.Ascorbate is not consumed during most catalytic cycles, but the enzymealso catalyzes decarboxylation of 2-oxoglutarate without subsequenthydroxylation, and ascorbate is required as a specific alternative oxygenacceptor in such uncoupled reaction cycles. A number of compounds inhibitprolyl 4-hydroxylase competitively with respect to some of itscosubstrates or the peptide substrate, and recently many suicideinactivators have also been described. Such inhibitors and inactivatorsare of considerable interest, because the prolyl 4-hydroxylase reactionwould seem a particularly suitable target for chemical regulation of theexcessive collagen formation found in patients with various fibroticdiseases. The active prolyl 4-hydroxylase ...
INTRODUCTION: Preterm cervical shortening and cervical insufficiency may be caused by a constitutional weakness of the cervix. The aim of this study was to assess the cervical collagen concentration in non-pregnant women with a history of cervical insufficiency or of a short cervix in the second trimester of pregnancy.. MATERIAL AND METHODS: In this case-control study we included non-pregnant women one year or more after pregnancy: 55 controls with a history of normal delivery; 27 women with a history of cervical insufficiency; and 10 women with a history of a short cervix (,5th percentile) and 10 women with a history of a long cervix (,95th percentile) at gestational weeks 18-20. We obtained biopsies (3 × 3-4 mm) from the ectocervix and determined the collagen concentration by measuring the hydroxyproline concentration.. RESULTS: Women with cervical insufficiency had lower collagen concentrations (63.5 ± 5.1%; mean ± SD) compared with controls (68.2 ± 5.4%; p = 0.0004); area under the ROC ...
Background: ACE inhibitors have shown beneficial results in several studies after myocardial infarction (MI). However, these studies have shown conflicting results about the ideal starting time of the ACE inhibitors administration after MI and the importance of infarct size.Objectives: This study was designed to assess the long-term effects of lisinopril on mortality, cardiac function, and ventricular fibrosis after MI, in rats.Methods: Lisinopril (20 mg/kg/day) was given on day 1 or 21 days after coronary occlusion in small or large infarctions.Results: the mortality rate was reduced by 39% in early treatment and 30% in delayed treatment in comparison to the untreated rats. Early treatment reduced cardiac dysfunction in small MIs; however, delayed treatment did not. No statistical difference was observed among the groups for large MIs. No statistical difference was observed among the groups with large or small MIs on myocardial hydroxyproline concentration.Conclusions: Both early and delayed ...
Members of this family belong to the collagen superfamily [(PUBMED:8240831)]. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The sequence is predominantly repeats of the G-X-Y and the polypeptide chains form a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxyproline. Collagens are post-translationally modified by proline hydroxylase to form the hydroxyproline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure.. ...
Results TRB3 expression was increased in fibroblasts of patients with SSc and in murine models of SSc in a transforming growth factor-β (TGF-β)/Smad-dependent manner. Overexpression of TRB3 stimulated canonical TGF-β signalling and induced an activated phenotype in resting fibroblasts. In contrast, knockdown of TRB3 reduced the profibrotic effects of TGF-β and decreased the collagen synthesis. Moreover, siRNA-mediated knockdown of TRB3 exerted potent antifibrotic effects and ameliorated bleomycin as well as constitutively active TGF-β receptor I-induced fibrosis with reduced dermal thickening, decreased hydroxyproline content and impaired myofibroblast differentiation. ...
Results Decreased expression of PARP1 was detected by immunohistochemistry in skin sections of SSc patients, particularly in fibroblasts. Inhibition of PARylation by 3AB augmented the stimulatory effects of TGFβ on fibroblasts in vitro. PARP1 inhibition increased Smad dependent transcription in reporter assays and promoted the transcription of TGFβ/Smad target genes. Treatment with 3AB also stimulated the collagen release and fostered the expression of contractile proteins with increased expression of α-smooth muscle actin (α-SMA) and enhanced formation of stress fiber formation compared to fibroblasts stimulated with TGFβ alone. Inhibition of PARylation also exacerbated experimental fibrosis in vivo. Treatment with 3AB induced a more severe fibrotic response to bleomycin with increased dermal thickening by up to 103% (p,0.0001), hydroxyproline contents and myofibroblast counts compared to control mice (p,0.0001 and p=0.0059). Inhibition of PARylation also strongly exacerbated fibrosis in ...
This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
The protein composition of Collagen Type I & III consist of nineteen amino acids responsible for growth and maintenance of the body with unusually high percentages of glycine, proline, hydroxyproline, all of which are found in the skin and muscle. This is what make Collagen M.D. Advanced Connective Tissue Formula effective in those areas. ...
Collagen is a protein made up of amino-acids, which are in turn built of carbon, oxygen and hydrogen. Collagen contains specific amino acids - Glycine, Proline, Hydroxyproline and Arginine.
Although the lung can regenerate after injury, repeated injury results in fibrosis, which compromises respiratory function. Cao et al. injected damaging chemicals into the tracheas of mice to investigate how fibrosis due to repetitive injury occurred. Mice receiving a single injection recovered blood oxygen concentration and exhibited re-epithelialization by type 1 alveolar cells and proliferation of the surfactant-producing type 2 alveolar epithelial cells. However, mice receiving repeated injections did not and, instead, had the sustained presence of protein markers of fibrosis (α-smooth muscle actin, collagen I, and hydroxyproline). Examination of Notch signaling, a regulator of lung fibroblasts, using transgenic Notch reporter mice revealed that Notch activation occurred in perivascular fibroblasts after repetitive injury. Repetitive lung injury resulted in an increase in the abundance of the Notch ligand Jagged1 (Jag1) in the pulmonary capillary endothelial cells (PCECs), which function ...
This product is rich in 18 kinds of amino acids human body required, including hydroxyproline, glycine, proline, which serves as function like protecting skins but can not be synthesized by our
antiarrhythmic peptide: atrial peptide from bovine atria; hexapeptide composed of hydroxyproline(1), proline(1), glycine(3) & alanine(1); both N-terminal & carboxy-terminal residues are glycine
Alpha Visage affects Face Wash Clean Face. I presume I need to find multitudes who have same interest in Alpha Visage. Each company has a different Alpha Visage scale and for that matter, a different way of Alpha Visage. Its the conclusion: There is very a bit implausible with what I am telling yo
|p||strong|SYIS AMPULKY PURE COLLAGEN 100% 10x3ML|/strong||/p| |p|Ampulka Collagen Pure 100% obsahuje |strong|rozpustný kolagén - soluble collagen|/strong| – ktorý zadržiava vodu v pokožke a chráni ju pred vznikom vr&aac
A colorimetric, soluble collagen assay for the analysis of acid and pepsin-soluble collagens produced in situ or during in-vitro cell culture.
Malotilate is a new drug suggested for use in chronic liver diseases. It is shown here to prevent liver damage caused by CCl4. The concomitant administration of malotilate with CCl4 significantly decreased hydroxyproline accumulation in the liver, liver prolyl 4-hydroxylase and liver and serum galactosylhydroxylysyl glucosyltransferase activities. However, it had no effect on the daily urinary hydroxyproline excretion or the hydroxyproline content of the skin, liver or lungs in normal young growing rats. It also had no specific inhibitory effect on hydroxyproline synthesis or secretion in fibroblast cultures, and did not affect the amount of procollagen-alpha 1(I)-specific mRNAs in these cultures. Thus it seems to have no direct inhibitory effect on collagen metabolism. In addition to inhibition of liver collagen accumulation, malotilate was also able to prevent the development of morphological changes in the liver such as focal necrosis, fatty infiltration and inflammatory changes. It also ...
Although widely used for its anti-estrogen properties tamoxifen has estrogen like effects on a number of tissues including bone and liver. Previous studies suggest a preservation of lumbar spine density in postmenopausal women but the effect on the hip had not been addressed. To determine whether tamoxifen prevents bone loss in the early postmenopausal period bone mineral density at the lumbar spine and femoral neck was measured using dual energy X-ray absorptiometry at presentation and 6 monthly thereafter for 1 year in a prospective controlled study. Also indices of bone turnover, serum osteocalcin and urinary hydroxyproline excretion, were assessed. Fifteen early postmenopausal women with Stage I or II breast cancer treated with tamoxifen and 21 normal postmenopausal women were studied. Sex hormone binding globulin and antithrombin III levels in serum were also measured as indices of the hepatic estrogenic activity. Tamoxifen (20 mg daily) prevented bone loss at the femoral neck and lumbar spine.
One obvious question raised is the origin of these amino acids. Under limited blood supply, two main sources of amino acids can be conceived: one is the degradation of extracellular matrix particularly by matrix metalloproteinases and the other is the autophagic degradation of preexisting intracellular proteins. In this perspective, it is notable that hydroxyproline concentration was significantly higher in tumor tissues than in their normal counterparts (P = 0.0005 in colon and P = 0.0025 in stomach tissues). Hydroxyproline is abundant in collagen and is posttranslationally produced from proline, which suggests that the higher concentration of hydroxyproline in tumor tissues is indicative of excess degradation of collagen ( 35). Autophagy is another possible source of amino acids, as it is well-documented that autophagy liberates and thereby increases the free amino acid pools ( 36, 37). We also have found recently that autophagy seems essential for colon cancer cell survival ( 38) and is ...
The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF) involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary fibrosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and plasminogen activator inhibitor-1 (PAI-1)
1. A partial amino acid sequence of 95 residues of the 191 residues in the oxidized A chain of human subcomponent C1q was determined. The partial nature of the sequence is because one overlapping peptide is missing in the proposed sequence, also the proof of some of the overlapping peptides depends partly on their amino acid composition and not on their complete sequence. 2. This region of the A chain contained a repeating sequence of glycine-X-Y (where X is often proline and Y is often hydroxyproline) for 78 residues. 3. The five hydroxylysine residues and the five hydroxyproline residues present in the oxidized A chain were all in these 78 residues and only in the Y position of the repeating sequence. 4. Prolonged collagenase digestion of the oxidized A chain yielded a large, apparently C-terminal, peptide which contained most of the non-collagenous sequences present in the chain. 5. It is concluded that there is a collagen-like region in the A chain of subcomponent C1q which constitutes most ...
The fouling marine mussel Mytilus edulis attaches itself to various substrates by spinning byssal threads, the adhesive discs of which are rich in the amino acid 3,4-dihydroxyphenylalanine (dopa). An acid-soluble protein was extracted and purified from the phenol gland located in the byssus-secreting foot of the animal. This protein is highly basic and contains large amounts of lysine, dopa, and 3- and 4-hydroxyproline. The composition of this protein and its sticky tendencies in vitro strongly suggest that it contributes to byssal adhesion.. ...
Abstract The collagen content of the liver, measured as hepatic hydroxyproline, was examined for a period of up to 52 weeks following Schistosoma mansoni infection. Hepatic fibrosis was much more marked in S. mansoni-infected mice of an outbred ICR strain than in C57BL/6J mice, while C3H/HeN mice occupied an intermediate position. The marked difference in hepatic fibrosis in ICR and C57BL/6J mice correlated with more rapid in vitro synthesis of collagen by the livers of infected ICR mice. Strains of mice exhibiting high and low levels of fibrosis provide an excellent tool for examining mechanisms of murine schistosomal hepatic fibrosis and its genetic regulation.
Dibutyltin dichloride (DBT}, one of a series of dialkyltin derivatives used industrially as polyvinylchloride stabilizers and urethane catalysts, was investigated for its ability to induce liver fibrosis in rats. Collagen, the predominant protein in fibrotic tissue, is synthesized in a series of sequential steps consisting of assembly of a proline-rich and lysine-rich polypeptide precursor of collagen, enzymatic hydroxylation of some of the prolyl and lysyl residues, and glycosylation of some of · the hydroxylysyl residues. Since prolyl residues are not hydroxylated before they are in peptide-bound form, the conversion of isotopically labeled proline to hydroxyproline by prolyl hydroxylase was taken as one parameter reflecting the rate of collagen formation. In vitro collagen synthesis was determined by incubation of liver biopsies with labeled proline, after which incorporation of label into collagenase digestible protein is compared to incorporation into collagenase- resistant protein. Hydroxyproline
Results DOCA-salt treatment for 5 weeks increased mean arterial pressure (MAP) determined by the telemetry system (144 ± 3 vs. 108 ± 4 mmHg, P , 0.01) and renal hypertrophy (116.3 ± 2.7 vs. 75.7 ± 1.4 mg/10 g of BW, P , 0.01) compared with sham mice. We also found that urinary 8-isoprostane and albumin excretion were increased in DOCA-salt mice compared with sham mice (1.76 ± 0.16 vs. 0.49 ± 0.10 ng/24 h; 41.1 ± 3.5 vs. 5.8 ± 0.6 μg/24 h, P , 0.05). Periodic acid-Schiff and Massons trichrome staining showed that DOCA-salt treatment caused obvious glomerulosclerosis and tubulointerstitial injury in the renal cortex (0.62 ± 0.06 vs. 0.08 ± 0.01; 3.00 ± 0.30 vs. 0.21 ± 0.10, P , 0.05), and tubulointerstitial fibrosis compared with the sham mice. Consistent with the results, renal collagen level determined using hydroxyproline assay was higher in DOCA-salt treated mice compared with the sham mice (26.8 ± 2.4 vs. 12.2 ± 1.3 μg/mg dry tissue, P , 0.05). In addition, F4/80-staining ...
Perhaps our most noteworthy finding is the demonstration of myocardial fibrosis after long-term, intensive exercise training. RV fibrosis was documented by collagen quantification in histological sections and analysis of hydroxyproline content. These observations were functionally paralleled by the development of RV diastolic dysfunction, with impaired relaxation potentially related to fibrotic infiltration. Moreover, we noted an increase in mRNA and protein expression of a series of fibrotic markers in the RV and in both atria. TGF-β1 expression was increased in the RA, LA, and RV after 16 weeks of intensive exercise. TGF-β1 is a potent stimulator of collagen-producing cardiac myofibroblasts22 and leads to fibrosis development. Experimental studies have reported that both genetic ablation of TGF-β1 in mice23 and treatment with anti-TGF-β1 antibodies24 inhibit fibrosis development, indicating that TGF-β1 plays a major role in collagen turnover. We also noted enhanced expression of other ...
Moreover, there are some collagen molecules containing sequences of hydrophobic amino acids inserted in the plasma membrane. For example, type XIII and XVII collagens. Collagen type XVII is part of the molecular structure of hemidesmosomes. No matter the type, collagen is synthesized inside the cell as a precursor: the pro-collagen molecule. First, alpha chains are synthesized in the endoplasmic reticulum, where proline becomes hydroxyproline by hydroxylation. Proline and hydroxyproline may be up to 20 % of the alpha chain. GLycosylation (type O-glycosylation) of alpha chains also occurs in the reticulum. At this point, three alpha chains join together by hydrogen bonds to finally form the pro-collagen molecule. Disulfide bridges are also formed between the alpha chains. Pro-collagen molecules are recognized and linked by transmembrane receptors and packaged in COPII coated vesicles. Typical COPII vesicles are 60 to 90 nm in diameter, but COPII vesicles transporting pro-collagen are 500 nm in ...
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