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PubMed1992

Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in periodontally healthy human subjects.

Age is known to be one of the factors which affect the rate of collagen and protein turnover in the connective tissues of the periodontium. The aim of the present study was to determine the levels of hydroxyproline (Hyp) and total protein in both the gingiva and gingival crevicular fluid (GCF) of periodontally healthy human subjects of two different age groups. The subjects of the young group were selected from among patients scheduled for extraction of upper and lower first or second premolars for orthodontic reasons. The second (older) group included individuals whose teeth were to be extracted for endodontic reasons. GCF was obtained before gingival sampling. The tissues surrounding the sockets were harvested immediately after extraction of the indicated teeth. All samples were analyzed biochemically. No significant difference was found in gingival and GCF levels of Hyp (which is unique to collagen) between the groups. Total protein levels in gingiva were significantly higher in the young group than in the older group. GCF total protein levels showed no significant difference between the groups. The higher gingival protein levels in the younger group seem to conform to previous findings.

Adolescent↗
PubMed1996

Hydroxyproline and total protein levels in gingiva from patients treated with phenytoin and cyclosporine-A.

Hydroxyproline (Hyp) and total protein levels were studied in gingiva from patients treated with phenytoin (PHT) and cyclosporine-A (CSA). The study included 5 groups of subjects: PHT and CSA groups with and without gingival overgrowth (PHT-GO+), (PHT-GO-), (CSA-GO+), (CSA-GO-), and periodontally healthy controls (C). After taking clinical measurements, gingival samples were harvested by gingivectomy or excising one or two papillae from the posterior areas. The samples were analyzed biochemically. In the PHT groups, both Hyp and total protein levels were significantly higher than in the C group. The differences between the PHT-GO+ and PHT-GO- groups were not statistically significant. In the CSA groups, total protein levels were significantly higher than in controls while no significant difference was found in Hyp levels. The differences between the CSA-GO+ and CSA-GO- groups were not statistically significant. When the PHT and CSA groups were compared, Hyp levels were significantly higher in the PHT-GO+ group than in the CSA-GO+ group. Total protein level differences between the PHT and CSA groups were not statistically significant. Correlations between age, plaque index, gingival overgrowth index, Hyp and total protein levels were analyzed and most were found not to be statistically significant. PHT appears to stimulate both collagen and total protein synthesis in gingiva while CSA seems to have a stronger effect on total protein synthesis. This suggests that the mechanisms underlying PHT- and CSA-induced gingival overgrowth are different and further comparative studies are needed.

Adult↗
PubMed1990

Intramuscular collagen and serum hydroxyproline as related to implanted testosterone, dihydrotestosterone and estradiol-17 beta in growing wethers.

Relationships of implanted testosterone, dihydrotestosterone and estradiol-17 beta to collagen degradation and intramuscular collagen concentration and stability were determined. Intramuscular collagen content, solubility and shrinkage temperature and serum hydroxyproline were analyzed in groups of six rams, wethers, and wethers implanted with various levels of testosterone or dihydrotestosterone and groups of 10 rams, wethers and wethers implanted with estradiol-17 beta, dihydrotestosterone or a combination of these two steroids. Intramuscular collagen content in both experiments was higher (P less than .05) in muscles of rams than in muscles of wethers. Administration of the highest level of testosterone to wethers raised (P less than .05) total and insoluble intramuscular collagen to concentrations noted in rams. Administration of the testosterone metabolite, dihydrotestosterone, to wethers had no effect on intramuscular collagen. Administration of estradiol-17 beta to wethers tended to raise concentrations of intramuscular collagen so that they were no longer lower (P less than .05) than those in rams. Collagen stability as measured by solubility and thermal shrinkage temperature did not differ among rams, wethers or implanted wethers (P greater than .05). Increases in collagen accretion due to hormone administration were observed to be the result of increases in the insoluble portion of the intramuscular collagen (P less than .05).

Animals↗
PubMed2005

Relationship between synovial fluid levels of glycosaminoglycans, hydroxyproline and general MMP activity and the presence and severity of articular cartilage change on the proximal articular surface of P1.

REASONS FOR PERFORMING STUDY: Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting horses and leads to degeneration of articular cartilage. Diagnosis is based on clinical signs in combination with radiography, which is relatively insensitive and provides only an indication of accumulated damage. Alternative methods, such as molecular markers, are therefore needed that can quantitatively, reliably and sensitively detect osteoarthritic changes in the joints at an early stage of the disease. If such markers are to be used reliably, it is important to know the relationship between marker concentration and cartilage composition. OBJECTIVES: To study the relationship between cartilage composition, synovial fluid levels of glycosaminoglycans (GAGs), hydroxyproline (Hyp) and general matrix metalloproteinase (MMP) activity, and the presence and severity of articular cartilage damage on the articular surface of P1. METHODS: Synovial fluid (SF) was collected from the metacarpophalangeal joints of 60 mature horses, and levels of GAGs, Hyp and general MMP activity were determined. Further, GAG and denatured collagen content of the articular cartilage were determined at the dorsal articular margin of P1 (site 1) and central cavity (site 2). The presence and severity of cartilage change was quantified using the cartilage degeneration index (CDI), measured at the same 2 sites. Correlations between SF parameters, cartilage composition and degree of cartilage degeneration were sought using correlation analysis. RESULTS: There was no correlation between GAG or Hyp content of SF and the amount of GAGs or denatured collagen, respectively, in cartilage. In joints with moderate to severe cartilage damage, the GAG content of site 1 was significantly lower than in joints with no to minimal cartilage change (P = 0.005) and there was a negative correlation between the amount of denatured collagen and GAG content at site 1 in all joints (r = -039, P = 0.002). Further, in joints with moderate to severe cartilage damage, there was a significant positive correlation between MMP activity in SF and Hyp levels in SF (r = 0.72, P < 0.001) and CDI at sites 1 (r = 0.46, P = 0.03) and 2 (r = 0.43, P = 0.04). CONCLUSIONS: General MMP activity in joints with moderate to severe cartilage damage is related to the severity of those cartilage changes and to Hyp levels in SF. Glycosaminoglycan levels in SF are not directly related to MMP activity, GAG content of articular cartilage or severity of cartilage change. POTENTIAL RELEVANCE: Glycosaminoglycan levels in SF are not helpful for the early detection of cartilage lesions. In damaged joints, Hyp levels may give an indication of the severity of cartilage change as they are strongly related to MMP activity, but do not qualify as markers for the presence or absence of cartilage lesions.

Age Factors↗
PubMed1979

The aortic content of glycosaminoglycans and hydroxyproline in experimental uraemia.

The effect of experimental renal failure in rats on the various glycosaminoglycan fractions and on the hydroxyproline content of the aorta was studied with special reference to the influence of parathyroidectomy. Renal failure increased those fractions which are known to contain chondroitin sulphate and dermatan sulphate. Parathyroidectomy did not modify these changes. Parathyroidectomy in rats with intact renal function produced an increase of the same fractions. It is concluded that accumulation of sulphated glycosaminoglycans is an early event in the development of uraemic arterial disease. The significance of such accumulation for subsequent development of arterial calcification is discussed. The available data do not permit evaluation of the significance of secondary hyperparathyroidism in the genesis of the observed changes of the glycosaminoglycans.

Animals↗
PubMed1987

Effects of cis-hydroxyproline on type II cell development in fetal rat lung.

The role of collagen in pulmonary epithelial cell division and differentiation during lung development was investigated by injecting the proline analogue cis-hydroxy-L-proline (cis-HYP) to timed pregnant rats. Lung weight, DNA and 3H thymidine incorporation were unchanged when compared to controls; epithelial cell division, determined by autoradiography, was also unchanged. However air sac development and phospholipid synthesis by epithelial cells were retarded in cis-HYP treated animals. The percentage of epithelial cells containing lamellar bodies was reduced at days 20-22 of gestation and the level of disaturated phosphatidylcholine (DSPC) was also significantly lower in treated rats. A sex-related difference was not eliminated by cis-HYP treatment, lung maturation was still more rapid in females. Non-dialysable hydroxyproline levels were decreased, and morphologically, less fibrillar collagen was seen at the epithelial-interstitial cell interface, though direct cell-cell contacts were not reduced. The results indicate that the injection of cis-HYP did not alter lung growth, but caused a reduction in fibrillar collagen which was associated with reduced surfactant synthesis by Type II epithelial cells.

Animals↗
PubMed1977

Isolation and purification of a small molecular weight hydroxyproline-containing structural glycopeptide from early mammalian granulation tissue.

A small molecular weight structural glycopeptide was solubilized after collagenase digestion of the connective tissue capsule surrounding the 5-day sponge-implant of the rat. The major amino acids are one residue each of aspartic and glutamic acids, proline, hydroxyproline and alanine and two residues of glycine, and the carbohydrates are one residue each of glucose, xylose and hexosamine and two residues of mannose. The sum of the amino acid and carbohydrate residues gives a molecular weight of 1635. Dansylation of the glycopeptide produces a single strongly fluorescent yellow-orange amino-terminal spot, not positively identified. The solubilization of the granuloma glycopeptide by collagenase and its composition are suggestive of its association with an immature form of collagen in early granulation tissue.

Amino Acids↗
PubMed1975

Effect of cortisone and an anabolic steroid upon plasma hydroxyproline during fracture healing in rabbits.

The effect of cortisone and an anabolic steroid on plasma hydroxyproline (HOP) was investigated in young male rabbits, following operative fracture of the radius. The action of these hormones was studied in three groups of animals, a cortisone (hydrocortisone sodium succinate 5mg/kg every day), an anabolic (norandronolone-19-phenylpropionate 5 mg/kg every other day) and a cortisone plus anabolic treated group. A fourth group of animals served as controls. Plasma HOP was found to increase during the fracture healing in control animals, particularly in the first week and during callus remodelling. Cortisone produced elevation of HOP level during the first two weeks followed by a decrease to low normal values. Animals treated with the anabolic did not present the initial rise but a sustained increase during callus remodelling. When both the anabolic and cortisone were administered, a curve similar to that of cortisone-treated animals was obtained. The initial increase of HOP is attributed to bone destruction and to a lesser degree to synchronous bone formation at the site of the fracture. This catabolic process seems to be enhanced by cortisone and inhibited by the anabolic. When, however, the two hormones are given together the protective anticatabolic effect of the anabolic is almost abolished.

Anabolic Agents↗
PubMed2006

Cis-hydroxyproline-induced inhibition of pancreatic cancer cell growth is mediated by endoplasmic reticulum stress.

AIM: To investigate the biological effects of cis-hydroxyproline (CHP) on the rat pancreatic carcinoma cell line DSL6A, and to examine the underlying molecular mechanisms. METHODS: The effect of CHP on DSL6A cell proliferation was assessed by using BrdU incorporation. The expression of focal adhesion kinase (FAK) was characterized by Western blotting and immunofluorescence. Induction of endoplasmic reticulum (ER) stress was investigated by using RT-PCR and Western blotting for the glucose-related protein-78 (GRP78) and growth arrest and DNA inducible gene (GADD153). Cell viability was determined through measuring the metabolic activity based on the reduction potential of DSL6A cells. Apoptosis was analyzed by detection of caspase-3 activation and cleavage of poly(ADP-ribose) polymerase (PARP) as well as DNA laddering. RESULTS: In addition to inhibition of proliferation, incubation with CHP induced proteolytic cleavage of FAK and a delocalisation of the enzyme from focal adhesions, followed by a loss of cell adherence. Simultaneously, we could show an increased expression of GRP78 and GADD153, indicating a CHP-mediated activation of the ER stress cascade in the DSL6A cell line. Prolonged incubation of DSL6A cells with CHP finally resulted in apoptotic cell death. Beside L-proline, the inhibition of intracellular proteolysis by addition of a broad spectrum protease inhibitor could abolish the effects of CHP on cellular functions and the molecular processes. In contrast, impeding the activity of apoptosis-executing caspases had no influence on CHP-mediated cell damage. CONCLUSION: Our data suggest that the initiation of ER stress machinery by CHP leads to an activation of intracellular proteolytic processes, including caspase-independent FAK degradation, resulting in damaging pancreatic carcinoma cells.

Animals↗
PubMed1997

[Evaluating clinical significance of tumor necrosis factor-alpha and hydroxyproline in blood of patients with active pulmonary tuberculosis].

OBJECTIVE: To evaluate the clinical significance of tumor necrosis factor-alpha (TNF-alpha) and hydroxyproline (HYP) in blood of patients with active pulmonary tuberculosis (APT). METHOD: Contents of TNF-alpha and HYP in blood of 28 patients with APT and 17 normal subjects were determined with enzyme-linked immunosorbent assay and ultraviolet spectrophotometer respectively. RESULT: It was found that the concentrations of TNF-alpha and HYP in patients with APT before antituberculosis treatment were obviously higher than those of the normal subjects (192.85 +/- 37.14 ng/L vs 89.36 +/- 23.18 ng/L and 4.96 +/- 1.13 mg/L vs 1.64 +/- 0.33 mg/L respectively, all P < 0.001) and those who received 3- month anti-tuberculosis treatment (192.65 +/- 37.14 ng/L vs 112.50 +/- 44.93 ng/L and 4.96 +/- 1.13 mg/L vs 2.17 +/- 0.39 mg/L respectively, all P < 0.001). TNF-alpha level was significantly correlated with HYP (r = 0.5132, P < 0.001). CONCLUSION: The results indicate that TNF-alpha might play an important role in inducing pulmonary tissue damage of APT, and the lowering of HYP content in blood might indicate that pulmonary tuberculosis is recovering from active stage.

Adolescent↗
PubMedDate not supplied

[Enthalpic denaturation of collagen satisfies the general relation of the change in Delta H(d) from Delta C(p) for proteins at zero hydroxyproline level].

One of the noticeable peculiarities of thermodynamics of collagen is an anomalous high magnitude of the enthalpy of denaturation delta Hd at a very low thermostability. Taking into account recent ideas about the role of hydrophobic interactions in determination of the thermodynamic function of protein denaturation, it is shown that the high magnitude of delta Hd of collagen in comparison with those of globular proteins can be explained by two factors: a significant contribution of residues of 4-hydroxyproline and small magnitude of hydrophobic interactions.

Collagen↗
PubMedDate not supplied

cis-hydroxyproline stimulates the growth of rat mammary carcinoma cells.

With the ever-increasing evidence that the extracellular matrix (ECM) can stimulate tumor growth, it follows that inhibiting the synthesis of tumor-derived stroma may be a potential therapeutic target of cancer progression. The proline analog cis-hydroxyproline (CHP), an inhibitor of collagen deposition, was examined for its effects on the growth of clonal tumor cells that differentially produce type IV collagen and laminin. Two separate clones derived from rat mammary carcinoma cells that produce high and low amounts of type IV collagen and laminin were injected into the flanks of nude mice. Tumors in animals receiving CHP treatment grew faster than tumors in control animals receiving saline, although statistically not significant. Furthermore, upon administration of CHP to these clones in culture, increased proliferation rates of both cell types were observed. These results show that CHP is not useful in preventing stromal development and growth of rat mammary tumor xenografts.

Animals↗
PubMed1979

[Collagen and hydroxyproline in carcass and skin of young rats fed with hypoproteic and hypocaloric diet].

The AA, reports the variations of collagen of carcass and skin of overnourished and proteic and caloric malnourished rats. The level of collagen is higher in malnourished when compared with normal and overnourished rats. The insoluble hydroxyproline concentration is higher in malnourished than in overnourished rats. This is reported to a variation of metabolic enzymatic patterns related to the catabolism of collagen.

Animals↗
PubMed1975

A column chromatography fractionation of the hydroxyproline-containing urinary peptides with continuous automatic detection.

Dialyzable and non-dialyzable urinary hydroxyproline-containing peptides are chromatographed respectively on QAE-Sephadex and on phosphocellulose. They are detected and quantitated by continuous hydrolysis in 3.3 N NaOH followed by oxidation by chloramine T and colorimetry with p-dimethylamino-benzaldehyde. The patterns of dialyzable urinary hypropeptides do not show significant qualitative differences between normal subjects and patients suffering from Paget's bone disease or cancer metastases of bone. The patterns of non-dialyzable urinary hypropeptides, show more variability in the case of normal subjects and differ more largely in the case of Paget's disease of bone.

Autoanalysis↗
PubMed1976

Urinary hydroxyproline values following continuous and intermittent administration of prednisolone in children.

The administration of 2 mg/kg body weight of prednisolone daily in divided doses to 5 healthy children aged 5-7 years resulted in a significant decrease in the amount of total urinary hydroxyproline (HOP) which was restored to pretreatment levels two weeks after discontinuation of the drug. On the other hand, the administration of 2 mg/kg body weight of prednisolone in a single dose on alternate days (every-other-day) to two children and for a period of 10 days caused insignificant alterations in the amount of urinary HOP.

Child↗
PubMed1976

Alaskan malamute chondrodysplasia. II. Urinary excretion of hydroxyproline, uronic acid and acid mucopolysaccharides.

The urinary excretion of free, total and non-dialyzable hydroxyproline appeared to be similar in both chondrodysplastic and non-chondrodysplastic Alaskan Malamutes of ages six and twenty-six weeks suggesting the metabolic defect was probably not related to a gross disturbance in collagen metabolism. Urinary hexuronic acids also appeared to be similar in levels for both populations. A four-fold increase in urinary mucopolysaccharide levels observed at age twenty-six weeks in the chondrodysplastic Alaskan Malamute suggested a deviation from normal. The magnitude and variability of deviation were not sufficient to indicate that this condition could serve as a model for the mucopolysaccharidosis of man but probably indicated a delayed maturation process.

Animals↗
PubMed1992

Bone-resorption markers galactosyl hydroxylysine, pyridinium crosslinks, and hydroxyproline compared.

We compared the clinical performances of four bone-resorption (BR) assays (hydroxyproline, HYP; galactosyl hydroxylysine, GHYL; deoxypyridinoline, DPD; and pyridinoline, PYD) in subjects with different BR rates: normal (adult men and premenopausal women), mildly increased (postmenopausal osteoporotic women), high (Paget disease patients), and very high (children). The discrimination power (Z score) and the accuracy (estimated by receiver-operating characteristic analysis) for GHYL, DPD, and PYD were compared with those for HYP. Discrimination power and accuracy were similar for high- and very-high-BR groups for all four assays. However in the mildly increased-BR group, DPD, GHYL, and PYD showed a higher discrimination power and accuracy than did HYP. The clinical performances of HYP, DPD, GHYL, and PYD are comparable for large changes in BR. For modest changes, DPD, GHYL, and PYD are more accurate and have a higher discrimination power than does HYP.

Adult↗