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Cell and Tissue Research Jan 2010The collagens represent a family of trimeric extracellular matrix molecules used by cells for structural integrity and other functions. The three alpha chains that form... (Review)
Review
The collagens represent a family of trimeric extracellular matrix molecules used by cells for structural integrity and other functions. The three alpha chains that form the triple helical part of the molecule are composed of repeating peptide triplets of glycine-X-Y. X and Y can be any amino acid but are often proline and hydroxyproline, respectively. Flanking the triple helical regions (i.e., Col domains) are non-glycine-X-Y regions, termed non-collagenous domains. These frequently contain recognizable peptide modules found in other matrix molecules. Proper tissue function depends on correctly assembled molecular aggregates being incorporated into the matrix. This review highlights some of the structural characteristics of collagen types I-XXVIII.
Topics: Amino Acid Motifs; Animals; Collagen; Humans; Hydroxyproline; Protein Structure, Tertiary; Structure-Activity Relationship
PubMed: 19693541
DOI: 10.1007/s00441-009-0844-4 -
Amino Acids Mar 2020Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-L-histidine), and... (Review)
Review
Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-L-histidine), and 4-hydroxyproline (an imino acid; also often referred to as an amino acid) were discovered in cattle, and the discovery of anserine (a methylated product of carnosine; β-alanyl-1-methyl-L-histidine) also originated with cattle. These five nutrients are highly abundant in beef, and have important physiological roles in anti-oxidative and anti-inflammatory reactions, as well as neurological, muscular, retinal, immunological and cardiovascular function. Of particular note, taurine, carnosine, anserine, and creatine are absent from plants, and hydroxyproline is negligible in many plant-source foods. Consumption of 30 g dry beef can fully meet daily physiological needs of the healthy 70-kg adult human for taurine and carnosine, and can also provide large amounts of creatine, anserine and 4-hydroxyproline to improve human nutrition and health, including metabolic, retinal, immunological, muscular, cartilage, neurological, and cardiovascular health. The present review provides the public with the much-needed knowledge of nutritionally and physiologically significant amino acids, dipeptides and creatine in animal-source foods (including beef). Dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline are beneficial for preventing and treating obesity, cardiovascular dysfunction, and ageing-related disorders, as well as inhibiting tumorigenesis, improving skin and bone health, ameliorating neurological abnormalities, and promoting well being in infants, children and adults. Furthermore, these nutrients may promote the immunological defense of humans against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of monocytes, macrophages, and other cells of the immune system. Red meat (including beef) is a functional food for optimizing human growth, development and health.
Topics: Animals; Anserine; Carnosine; Cattle; Creatine; Humans; Hydroxyproline; Nutritive Value; Red Meat; Taurine
PubMed: 32072297
DOI: 10.1007/s00726-020-02823-6 -
The European Respiratory Journal May 2022Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with few treatment options. The poor success in developing anti-IPF strategies has impelled researchers to...
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with few treatment options. The poor success in developing anti-IPF strategies has impelled researchers to reconsider the importance of the choice of animal model and assessment methodologies. Currently, it is still not settled whether the bleomycin-induced lung fibrosis mouse model finally returns to resolution.
METHODS
This study aimed to follow the dynamic fibrotic features of bleomycin-treated mouse lungs over extended durations through a combination of the latest technologies (micro-computed tomography imaging and histological detection of degraded collagens) and traditional methods. In addition, we also applied immunohistochemistry to explore the distribution of all hydroxyproline-containing molecules.
RESULTS
As determined by classical biochemical methods, total lung hydroxyproline contents reached a peak at 4 weeks after bleomycin injury and maintained a steady high level thereafter until the end of the experiments (16 weeks). This result seemed to partially contradict with the changes of other fibrosis evaluation parameters, which indicated a gradual degradation of collagens and a recovery of lung aeration after the fibrosis peak. This inconsistency was well reconciled by our data from immunostaining against hydroxyproline and fluorescent peptide staining against degraded collagen, together showing large amounts of hydroxyproline-rich degraded collagen fragments detained and enriched within the intracellular regions at 10 or 16 weeks rather than at 4 weeks after bleomycin treatment.
CONCLUSIONS
Our present data not only offer respiratory researchers a new perspective towards the resolution nature of mouse lung fibrosis, but also remind them to be cautious when using the hydroxyproline content assay to evaluate the severity of fibrosis.
Topics: Animals; Bleomycin; Collagen; Disease Models, Animal; Humans; Hydroxyproline; Idiopathic Pulmonary Fibrosis; Lung; Mice; Mice, Inbred C57BL; X-Ray Microtomography
PubMed: 34561295
DOI: 10.1183/13993003.00864-2021 -
Ecotoxicology and Environmental Safety Oct 2022Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic...
Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1β, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-β1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway.
Topics: Animals; Fibrosis; Hydroxyproline; Interleukin-18; Janus Kinase 2; Macrophages; Pneumonia; Pulmonary Fibrosis; Pyridones; RNA, Messenger; Rats; Signal Transduction; Silicosis; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Vimentin
PubMed: 36108436
DOI: 10.1016/j.ecoenv.2022.114066 -
Critical Reviews in Biochemistry and... Apr 2010Posttranslational modifications can cause profound changes in protein function. Typically, these modifications are reversible, and thus provide a biochemical on-off... (Review)
Review
Posttranslational modifications can cause profound changes in protein function. Typically, these modifications are reversible, and thus provide a biochemical on-off switch. In contrast, proline residues are the substrates for an irreversible reaction that is the most common posttranslational modification in humans. This reaction, which is catalyzed by prolyl 4-hydroxylase (P4H), yields (2S,4R)-4-hydroxyproline (Hyp). The protein substrates for P4Hs are diverse. Likewise, the biological consequences of prolyl hydroxylation vary widely, and include altering protein conformation and protein-protein interactions, and enabling further modification. The best known role for Hyp is in stabilizing the collagen triple helix. Hyp is also found in proteins with collagen-like domains, as well as elastin, conotoxins, and argonaute 2. A prolyl hydroxylase domain protein acts on the hypoxia inducible factor alpha, which plays a key role in sensing molecular oxygen, and could act on inhibitory kappaB kinase and RNA polymerase II. P4Hs are not unique to animals, being found in plants and microbes as well. Here, we review the enzymic catalysts of prolyl hydroxylation, along with the chemical and biochemical consequences of this subtle but abundant posttranslational modification.
Topics: Animals; Collagen; Humans; Hydroxylation; Hydroxyproline; Procollagen-Proline Dioxygenase; Proline; Protein Processing, Post-Translational; Species Specificity; Substrate Specificity
PubMed: 20199358
DOI: 10.3109/10409231003627991 -
Archives of Disease in Childhood Dec 1968
Topics: Amino Acid Metabolism, Inborn Errors; Diet Therapy; Humans; Hydroxyproline; Infant; Male; Proline
PubMed: 5702251
DOI: 10.1136/adc.43.232.748-a -
Journal of Bacteriology Feb 2016Sinorhizobium meliloti forms N2-fixing root nodules on alfalfa, and as a free-living bacterium, it can grow on a very broad range of substrates, including l-proline and...
UNLABELLED
Sinorhizobium meliloti forms N2-fixing root nodules on alfalfa, and as a free-living bacterium, it can grow on a very broad range of substrates, including l-proline and several related compounds, such as proline betaine, trans-4-hydroxy-l-proline (trans-4-l-Hyp), and cis-4-hydroxy-d-proline (cis-4-d-Hyp). Fourteen hyp genes are induced upon growth of S. meliloti on trans-4-l-Hyp, and of those, hypMNPQ encodes an ABC-type trans-4-l-Hyp transporter and hypRE encodes an epimerase that converts trans-4-l-Hyp to cis-4-d-Hyp in the bacterial cytoplasm. Here, we present evidence that the HypO, HypD, and HypH proteins catalyze the remaining steps in which cis-4-d-Hyp is converted to α-ketoglutarate. The HypO protein functions as a d-amino acid dehydrogenase, converting cis-4-d-Hyp to Δ(1)-pyrroline-4-hydroxy-2-carboxylate, which is deaminated by HypD to α-ketoglutarate semialdehyde and then converted to α-ketoglutarate by HypH. The crystal structure of HypD revealed it to be a member of the N-acetylneuraminate lyase subfamily of the (α/β)8 protein family and is consistent with the known enzymatic mechanism for other members of the group. It was also shown that S. meliloti can catabolize d-proline as both a carbon and a nitrogen source, that d-proline can complement l-proline auxotrophy, and that the catabolism of d-proline is dependent on the hyp cluster. Transport of d-proline involves the HypMNPQ transporter, following which d-proline is converted to Δ(1)-pyrroline-2-carboxylate (P2C) largely via HypO. The P2C is converted to l-proline through the NADPH-dependent reduction of P2C by the previously uncharacterized HypS protein. Thus, overall, we have now completed detailed genetic and/or biochemical characterization of 9 of the 14 hyp genes.
IMPORTANCE
Hydroxyproline is abundant in proteins in animal and plant tissues and serves as a carbon and a nitrogen source for bacteria in diverse environments, including the rhizosphere, compost, and the mammalian gut. While the main biochemical features of bacterial hydroxyproline catabolism were elucidated in the 1960s, the genetic and molecular details have only recently been determined. Elucidating the genetics of hydroxyproline catabolism will aid in the annotation of these genes in other genomes and metagenomic libraries. This will facilitate an improved understanding of the importance of this pathway and may assist in determining the prevalence of hydroxyproline in a particular environment.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Hydroxyproline; Models, Molecular; Molecular Structure; Oxidoreductases Acting on CH-NH Group Donors; Proline; Protein Conformation; Recombinant Proteins; Sinorhizobium meliloti
PubMed: 26833407
DOI: 10.1128/JB.00961-15 -
Clinical and Experimental Dental... Oct 2021Odontogenic tumors are relatively common oro-facial tumors seen in our environment with challenges encountered with management in terms of inadequate infrastructure and...
BACKGROUND
Odontogenic tumors are relatively common oro-facial tumors seen in our environment with challenges encountered with management in terms of inadequate infrastructure and high cost of treatment. They are often associated with bone resorption with concomitant collagen degradation and excretion of their by-products in serum or urine. The aim of this present study was to evaluate urinary hydroxyproline level in patients with benign mandibular odontogenic tumors.
MATERIALS AND METHODS
Twenty-two consecutive patients with histologically diagnosed mandibular odontogenic tumors were recruited. Twenty-two controls who matched the study group for sex and age were also recruited. The study group had CT-Scan of their lesions done. All participants were required to fast 12 hours overnight and their early morning second void urine collected between 7 a.m and 8 a.m. The collected urine samples were stored frozen at -20°C until analysis. Colorimetric method of analysis of urinary hydroxyproline and creatinine were done using Biovision hydroxyproline kit and Randox creatinine kit, respectively. The results were recorded as urinary hydroxyproline alone (μg/μl) and as urinary hydroxyproline/creatinine ratio.
RESULTS
The mean age of the participants was 28.45 ± 6.8 years. The mean duration of the tumors in the study group was 5.9 ± 4.4 years. A mean urinary hydroxyproline/ creatinine ratio of 0.081 ± 0.129 was noted in the study group as compared to 0.016 ± 0.006 that was noted among healthy Nigerian who served as controls in the study.
CONCLUSION
There was a significant increase in urinary hydroxyproline level in patients with odontogenic tumors when compared with healthy Nigerians.
Topics: Adult; Creatinine; Humans; Hydroxyproline; Odontogenic Tumors; Young Adult
PubMed: 33496059
DOI: 10.1002/cre2.392 -
Essays in Biochemistry Sep 2019Co- and post-translational hydroxylation of proline residues is critical for the stability of the triple helical collagen structure. In this review, we summarise the... (Review)
Review
Co- and post-translational hydroxylation of proline residues is critical for the stability of the triple helical collagen structure. In this review, we summarise the biology of collagen prolyl 4-hydroxylases and collagen prolyl 3-hydroxylases, the enzymes responsible for proline hydroxylation. Furthermore, we describe the potential roles of hydroxyproline residues in the complex interplay between collagens and other proteins, especially integrin and discoidin domain receptor type cell adhesion receptors. Qualitative and quantitative regulation of collagen hydroxylation may have remarkable effects on the properties of the extracellular matrix and consequently on the cell behaviour.
Topics: Animals; Collagen; Humans; Hydroxylation; Hydroxyproline; Integrins; Procollagen-Proline Dioxygenase; Protein Binding; Protein Processing, Post-Translational; Protein Structure, Quaternary
PubMed: 31350381
DOI: 10.1042/EBC20180053 -
Bioengineered 2014Mammalian collagen has been widely used as a biomedical material. Nevertheless, there are still concerns about the variability between preparations, particularly with... (Review)
Review
Mammalian collagen has been widely used as a biomedical material. Nevertheless, there are still concerns about the variability between preparations, particularly with the possibility that the products may transmit animal-based diseases. Many groups have examined the possible application of bioengineered mammalian collagens. However, translating laboratory studies into large-scale manufacturing has often proved difficult, although certain yeast and plant systems seem effective. Production of full-length mammalian collagens, with the required secondary modification to give proline hydroxylation, has proved difficult in E. coli. However, recently, a new group of collagens, which have the characteristic triple helical structure of collagen, has been identified in bacteria. These proteins are stable without the need for hydroxyproline and are able to be produced and purified from E. coli in high yield. Initial studies indicate that they would be suitable for biomedical applications.
Topics: Bacterial Proteins; Biocompatible Materials; Biomedical and Dental Materials; Collagen; Hydroxyproline; Protein Engineering; Recombinant Proteins
PubMed: 24717980
DOI: 10.4161/bioe.28791