Proline-dependent regulation of collagen metabolism

Karna, Ewa; Szoka, Łukasz; Huynh, Thi Yen Ly; Pałka, Jerzy

doi:10.1007/s00018-019-03363-3

Cited by 132 publications

(86 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, the difference between the groups were most prominent during sleep (at 5 a.m.). It is well established that Pro constitutes about 10% of total amino acids in collagens and is thus essential for the biosynthesis of collagen 14 . The small intestine takes up considerable loads of dietary proline 14,15 .…”

Section: Resultsmentioning

confidence: 99%

“…It is well established that Pro constitutes about 10% of total amino acids in collagens and is thus essential for the biosynthesis of collagen 14 . The small intestine takes up considerable loads of dietary proline 14,15 . Tissue segments of pharyngeal muscles have been demonstrated to contain significantly more collagen I in OSA patients than in controls 16 .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

“The Effect of Obstructive Sleep Apnea on Peripheral Blood Amino Acid and Biogenic Amine Metabolome at Multiple Time Points Overnight“

Kiens

Taalberg

Иванова

et al. 2020

Preprint

View full text Add to dashboard Cite

There are no clinical studies that have investigated the differences in blood serum metabolome between obstructive sleep apnea (OSA) patients and controls. In a single-center prospective observational study, we compared metabolomic profiles in the peripheral blood of OSA patients with apnea-hypopnea index (AHI) > 15/h and control individuals. Blood was obtained at 3 different time points overnight: 21:00 p.m.; 5:00 a.m. and 7:00 a.m. We used a targeted approach for detecting amino acids and biogenic amines and analyzed the data with ranked general linear model for repeated measures. We recruited 31 patients with moderate-to-severe OSA and 32 controls. Significant elevations in median concentrations of alanine, proline and kynurenine in OSA patients compared to controls were detected. Significant changes in the overnight dynamics of peripheral blood concentrations occurred in OSA: glutamine, serine, threonine, tryptophan, kynurenine and glycine levels increased, whereas a fall occurred in the same biomarker levels in controls. Phenylalanine and proline levels decreased slightly, compared to a steeper fall in controls. The study indicates that serum profiles of amino acid and biogenic amines are significantly altered in patients with OSA referring to vast pathophysiologic shifts reflected in the systemic metabolism.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“The Effect of Obstructive Sleep Apnea on Peripheral Blood Amino Acid and Biogenic Amine Metabolome at Multiple Time Points Overnight“

Kiens

Taalberg

Иванова

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…It is known that the addition of PRO to medium or the rise in its extracellular concentration had a small, but significant, effect on in vitro collagen biosynthesis by fibroblasts. On the other hand, it was found that there was a strong positive effect of extracellular PRO on collagen biosynthesis when insufficient endogenous synthesis of PRO occurred from substrates, such as glutamine [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…In collagen, HYP is produced via hydroxylation of proline (PRO) in pro-collagen fibers [ 33 ]. On the other hand, PRO, as one of the basic amino acids in collagen, is synthesized in mammals from arginine via arginase I or II [ 34 ] or the glutamine pathway [ 35 ]. Glycine (GLY) had a strong effect on the expression of the calcified chondrocyte osteopontin marker with calcification of chondrocytes, while no similar effect on osteoblasts was found [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Properties, In Vitro and In Vivo Evaluation of Calcium Phosphate/Amino Acid Cements for Treatment of Osteochondral Defects

et al. 2021

View full text Add to dashboard Cite

Novel calcium phosphate cements containing a mixture of four amino acids, glycine, proline, hydroxyproline and either lysine or arginine (CAL, CAK) were characterized and used for treatment of artificial osteochondral defects in knee. It was hypothesized that an enhanced concentration of extracellular collagen amino acids (in complex mixture), in connection with bone cement in defect sites, would support the healing of osteochondral defects with successful formation of hyaline cartilage and subchondral bone. Calcium phosphate cement mixtures were prepared by in situ reaction in a planetary ball mill at aseptic conditions and characterized. It was verified that about 30–60% of amino acids remained adsorbed on hydroxyapatite particles in cements and the addition of amino acids caused around 60% reduction in compressive strength and refinement of hydroxyapatite particles in their microstructure. The significant over-expression of osteogenic genes after the culture of osteoblasts was demonstrated in the cement extracts containing lysine and compared with other cements. The cement pastes were inserted into artificial osteochondral defects in the medial femoral condyle of pigs and, after 3 months post-surgery, tissues were analyzed macroscopically, histologically, immunohistochemically using MRI and X-ray methods. Analysis clearly showed the excellent healing process of artificial osteochondral defects in pigs after treatment with CAL and CAK cements without any inflammation, as well as formation of subchondral bone and hyaline cartilage morphologically and structurally identical to the original tissues. Good integration of the hyaline neocartilage with the surrounding tissue, as well as perfect interconnection between the neocartilage and new subchondral bone tissue, was demonstrated. Tissues were stable after 12 months’ healing.

show abstract

“…9 & Supplemental Table 2). Given the necessity of glutamate in ECM remodeling, it is probable that glutamate is being diverted to collagen synthesis (as reviewed in Karna, et al 2020 [76]). In addition to active glycolysis, an observed shift to the PPP via glucuronate and the accumulation of UDP-glucuronate (Fig.…”

Section: Discussionmentioning

confidence: 99%

Integrated Metabolomics, Transcriptomics, and Signal Protein Profile Define the Effector Function and Associated Metabotype of Five Polarized Macrophage Phenotypes

et al. 2020

Preprint

View full text Add to dashboard Cite

As of 2013, there were nearly 30 million Americans with diabetes or one in ten adults, but by 2050, estimates from the American Diabetes Association indicate that one in three adults (~350 million Americans) will be diabetic. At current rates of amputation (~25%) due to non-healing wounds, this 2050 population will have to absorb the social and economic burden of over 85 million diabetic amputees. While normal wound healing proceeds through a well-described iterative process, in non-healing wounds this process stalls at the transition from inflammation to tissue repair. Our central hypothesis is that macrophage plasticity is key to this transition and directly facilitates shifting the wound environment from pro-inflammatory to promoting tissue repair. While more established signaling molecules of immunity (such as cytokines and chemokines) remain essential to driving functional phenotype in the immune system, recent advances in metabolomics profiling have revealed a pivotal role for metabolites in immunomodulation. Presented herein, an ex vivo macrophage culture model produces five macrophage functional phenotypes compared to the parent resting macrophage phenotype and is a systems-level model for understanding the contribution of metabolism to macrophage functional plasticity.Specifically, CD14+ peripheral blood monocytes are isolated, differentiated into M0 macrophages, and polarized into the M1 (IFN-gamma;/LPS), M2a (IL-4/IL-13), M2b (IC/LPS), M2c (IL-10), and M2d (IL-6/LIF) phenotypes. Each phenotype is then characterized by a bioanalyte matrix of four cell surface markers, ~50 secreted immunomodulating proteins (cytokines, chemokines, and growth factors), ~800 myeloid genes, and ~450 identified metabolites (including lipids). Signal protein profiles and pathway enrichment analysis of expressed genes generally groups the phenotypes into pro-inflammatory (M1 and M2b) and tissue repair/regenerative (M2a, M2c, and M2d); however, clear distinctions between each phenotype can be made.For example, M1 macrophages activate processes that facilitate acute inflammatory responses through control of nitric oxide (NO) and reactive oxygen species (ROS), whereas M2b macrophages activate processes that regulate chronic inflammation and chemotaxis of lymphocytes, endothelial cells, and epithelial cells.Furthermore, both M2c and M2d macrophages activate angiogenesis processes, but M2c macrophages promote extracellular matrix (ECM) assembly while M2d macrophages activate processes that drive ECM degradation.Finally, metabolomics profiles further validate recent findings that shifts between aerobic glycolysis, the pentose phosphate pathway, and oxidative phosphorylation distinguish pro-inflammatory macrophages and tissue repair/regeneration macrophages; however, our model provides further evidence to support the association between metabolism (such as decoupling of the TCA cycle, fatty acid synthesis, and -oxidation) and functional phenotype. Metabolomics is fundamentally changing our understanding of immunomodulation in diverse...

show abstract

Proline-dependent regulation of collagen metabolism

Cited by 132 publications

References 90 publications

“The Effect of Obstructive Sleep Apnea on Peripheral Blood Amino Acid and Biogenic Amine Metabolome at Multiple Time Points Overnight“

“The Effect of Obstructive Sleep Apnea on Peripheral Blood Amino Acid and Biogenic Amine Metabolome at Multiple Time Points Overnight“

Characterization of Properties, In Vitro and In Vivo Evaluation of Calcium Phosphate/Amino Acid Cements for Treatment of Osteochondral Defects

Integrated Metabolomics, Transcriptomics, and Signal Protein Profile Define the Effector Function and Associated Metabotype of Five Polarized Macrophage Phenotypes

Contact Info

Product

Resources

About