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European Respiratory Review : An... Jun 2018Matrikines are bioactive fragments of the extracellular matrix (ECM) that are fundamental in regulating a diverse array of physiological processes. The tripeptide... (Review)
Review
Matrikines are bioactive fragments of the extracellular matrix (ECM) that are fundamental in regulating a diverse array of physiological processes. The tripeptide Proline-Glycine-Proline (PGP) is a collagen-derived matrikine that has classically been described as a neutrophil chemoattractant. In this article, we describe our current understanding of the pathways that generate, degrade and modify PGP to dictate its bioavailability and stability. Additionally, we discuss our expanding appreciation of the capacity of PGP to regulate diverse cell types and biological processes, independent of its activity on neutrophils, including a putative role in wound repair. We argue that PGP functions as a primitive and conserved damage-associated molecular pattern, which is generated during infection or injury and subsequently acts to shape ensuing inflammatory and repair processes. As a fragment of the ECM that accumulates at the epicentre of the action, PGP is perfectly positioned to focus neutrophils to the exact site required and direct a localised repair response. However, it is essential that PGP is efficiently degraded, as if this matrikine is allowed to persist then pathology can ensue. Accordingly, we discuss how this pathway is subverted in chronic lung diseases giving rise to persistent inflammation and pathological tissue remodelling.
Topics: Airway Remodeling; Animals; Collagen; Extracellular Matrix; Humans; Lung; Lung Diseases; Neutrophil Infiltration; Oligopeptides; Peptide Fragments; Proline; Signal Transduction
PubMed: 29950303
DOI: 10.1183/16000617.0017-2018 -
Frontiers in Bioscience (Landmark... Jun 2023Intrinsically disordered proteins and protein regions (IDPs/IDRs) are important in diverse biological processes. Lacking a stable secondary structure, they display an...
BACKGROUND
Intrinsically disordered proteins and protein regions (IDPs/IDRs) are important in diverse biological processes. Lacking a stable secondary structure, they display an ensemble of conformations. One factor contributing to this conformational heterogeneity is the proline isomerization. The knowledge and value of a given proline ratio are paramount, as the different conformational states can be responsible for different biological functions. Nuclear Magnetic Resonance (NMR) spectroscopy is the only method to characterize the two co-existing isomers on an atomic level, and only a few works report on these data.
METHODS
After collecting the available experimental literature findings, we conducted a statistical analysis regarding the influence of the neighboring amino acid types ( ± 4 regions) on forming a -Pro isomer. Based on this, several regularities were formulated. NMR spectroscopy was then used to define the Pro content on model peptides and desired point mutations.
RESULTS
Analysis of NMR spectra prove the dependence of the Pro content on the type of the neighboring amino acid-with special attention on aromatic and positively charged sidechains.
CONCLUSIONS
Our results may benefit the design of protein regions with a given -Pro content, and contribute to a better understanding of the roles and functions of IDPs.
Topics: Isomerism; Intrinsically Disordered Proteins; Proline; Peptides; Magnetic Resonance Spectroscopy; Protein Conformation
PubMed: 37395034
DOI: 10.31083/j.fbl2806127 -
Cells Mar 2021The study examines the effect of acclimation on the antioxidant system and proline metabolism in cucumber leaves subjected to 100 and 150 NaCl stress. The levels of...
The study examines the effect of acclimation on the antioxidant system and proline metabolism in cucumber leaves subjected to 100 and 150 NaCl stress. The levels of protein carbonyl group, thiobarbituric acid reactive substances, α-tocopherol, and activity of ascorbate and glutathione peroxidases, catalase, glutathione -transferase, pyrroline-5-carboxylate: synthetase and reductase as well as proline dehydrogenase were determined after 24 and 72 h periods of salt stress in the acclimated and non-acclimated plants. Although both groups of plants showed high α-tocopherol levels, in acclimated plants was observed higher constitutive concentration of these compounds as well as after salt treatment. Furthermore, the activity of enzymatic antioxidants grew in response to salt stress, mainly in the acclimated plants. In the acclimated plants, protein carbonyl group levels collapsed on a constitutive level and in response to salt stress. Although both groups of plants showed a decrease in proline dehydrogenase activity, they differed with regard to the range and time. Differences in response to salt stress between the acclimated and non-acclimated plants may suggest a relationship between increased tolerance in acclimated plants and raised activity of antioxidant enzymes, high-level of α-tocopherol as well, as decrease enzyme activity incorporates in proline catabolism.
Topics: Antioxidants; Cucumis sativus; Humans; Plant Leaves; Proline; Salt Stress
PubMed: 33801884
DOI: 10.3390/cells10030609 -
Biochemistry Feb 2020Pancreatic amyloid formation by the polypeptide IAPP contributes to β-cell dysfunction in type 2 diabetes. There is a 1:1 correspondence between the ability of IAPP...
Pancreatic amyloid formation by the polypeptide IAPP contributes to β-cell dysfunction in type 2 diabetes. There is a 1:1 correspondence between the ability of IAPP from different species to form amyloid and the susceptibility of the organism to develop diabetes. Rat IAPP is non-amyloidogenic and differs from human IAPP at six positions, including three proline replacements: A25P, S28P, and S29P. Incorporation of these proline residues into human IAPP leads to a non-amyloidogenic analogue that is used clinically. The role of the individual proline residues is not understood. We examine the three single and three double proline substitutions in the context of human IAPP. An S28P substitution significantly decreases amyloidogenicity and toxicity, while an S29P substitution has very modest effects despite being an identical replacement just one residue away. The consequences of the A25P substitution are between those of the two Ser to Pro substitutions. Double analogues containing an S28P replacement are less amyloidogenic and less toxic than the IAPP double analogue. Ion mobility mass spectrometry reveals that there is no correlation between the monomer or dimer conformation as reported by collision cross section measurements and the time to form amyloid. The work reveals both the plasticity of IAPP amyloid formation and the exquisite sequence sensitivity of IAPP amyloidogenicity and toxicity. The study highlights the key role of the S28P substitution and provides information that will aid in the rational design of soluble variants of IAPP. The variants studied here offer a system for further exploring features that control IAPP toxicity.
Topics: Algorithms; Amino Acid Sequence; Amino Acid Substitution; Amyloid; Genetic Variation; Humans; Islet Amyloid Polypeptide; Proline
PubMed: 31922743
DOI: 10.1021/acs.biochem.9b01109 -
Molecular and Cellular Biochemistry Mar 2020In stress conditions, as neoplastic transformation, amino acids serve not only as nutrients to maintain the cell survival but also as mediators of several regulatory... (Review)
Review
Understanding the role of key amino acids in regulation of proline dehydrogenase/proline oxidase (prodh/pox)-dependent apoptosis/autophagy as an approach to targeted cancer therapy.
In stress conditions, as neoplastic transformation, amino acids serve not only as nutrients to maintain the cell survival but also as mediators of several regulatory pathways which are involved in apoptosis and autophagy. Especially, under glucose deprivation, in order to maintain the cell survival, proline and glutamine together with other glutamine-derived products such as glutamate, alpha-ketoglutarate, and ornithine serve as alternative sources of energy. They are substrates for production of pyrroline-5-carboxylate which is the product of conversion of proline by proline dehydrogenase/ proline oxidase (PRODH/POX) to produce ATP for protective autophagy or reactive oxygen species for apoptosis. Interconversion of proline, ornithine, and glutamate may therefore regulate PRODH/POX-dependent apoptosis/autophagy. The key amino acid is proline, circulating between mitochondria and cytoplasm in the proline cycle. This shuttle is known as proline cycle. It is coupled to pentose phosphate pathway producing nucleotides for DNA biosynthesis. PRODH/POX is also linked to p53 and AMP-activated protein kinase (AMPK)-dependent pathways. Proline availability for PRODH/POX-dependent apoptosis/autophagy is regulated at the level of collagen biosynthesis (proline utilizing process) and prolidase activity (proline supporting process). In this review, we suggest that amino acid metabolism linking TCA and Urea cycles affect PRODH/POX-dependent apoptosis/autophagy and the knowledge might be useful to targeted cancer therapy.
Topics: Apoptosis; Autophagy; Humans; Neoplasm Proteins; Neoplasms; Proline; Proline Oxidase; Signal Transduction
PubMed: 31933109
DOI: 10.1007/s11010-020-03685-y -
Nature Dec 2018Deconstructive functionalization involves carbon-carbon (C-C) bond cleavage followed by bond construction on one or more of the constituent carbons. For example,...
Deconstructive functionalization involves carbon-carbon (C-C) bond cleavage followed by bond construction on one or more of the constituent carbons. For example, ozonolysis and olefin metathesis have allowed each carbon in C=C double bonds to be viewed as a functional group. Despite the substantial advances in deconstructive functionalization involving the scission of C=C double bonds, there are very few methods that achieve C(sp)-C(sp) single-bond cleavage and functionalization, especially in relatively unstrained cyclic systems. Here we report a deconstructive strategy to transform saturated nitrogen heterocycles such as piperidines and pyrrolidines, which are important moieties in bioactive molecules, into halogen-containing acyclic amine derivatives through sequential C(sp)-N and C(sp)-C(sp) single-bond cleavage followed by C(sp)-halogen bond formation. The resulting acyclic haloamines are versatile intermediates that can be transformed into various structural motifs through substitution reactions. In this way we achieve the skeletal remodelling of cyclic amines, an example of scaffold hopping. We demonstrate this deconstructive strategy by the late-stage diversification of proline-containing peptides.
Topics: Alkenes; Amines; Carbon; Chlorine; Cyclization; Nitrogen; Peptides; Piperidines; Proline; Pyrrolidines
PubMed: 30382193
DOI: 10.1038/s41586-018-0700-3 -
Plant Physiology and Biochemistry : PPB Jun 2017Major abiotic stress factors such as salt and drought adversely affect important physiological processes and biochemical mechanisms and cause severe loss in crop... (Review)
Review
Major abiotic stress factors such as salt and drought adversely affect important physiological processes and biochemical mechanisms and cause severe loss in crop productivity worldwide. Plants develop various strategies to stand healthy against these stress factors. The accumulation of proline (Pro) is one of the striking metabolic responses of plants to salt and drought stress. Pro biosynthesis and signalling contribute to the redox balance of cell under normal and stressful conditions. However, literature is meager on the sustainable strategies potentially fit for modulating Pro biosynthesis and production in stressed plants. Considering the recent literature, this paper in its first part overviews Pro biosynthesis and transport in plants and also briefly highlights the significance of Pro in plant responses to salt and drought stress. Secondly, this paper discusses mechanisms underlying the regulation of Pro metabolism in salt and drought-exposed plant via phytohormones, mineral nutrients and transgenic approaches. The outcome of the studies may give new opportunities in modulating Pro metabolism for improving plant tolerance to salt and drought stress and benefit sustainable agriculture.
Topics: Droughts; Minerals; Plant Growth Regulators; Plants; Proline; Salt Tolerance
PubMed: 28364709
DOI: 10.1016/j.plaphy.2017.03.018 -
Molecules (Basel, Switzerland) Oct 2022An efficient way to access highly functionalized proline derivatives was developed based on a Cu(I)-catalyzed reaction between CF-substituted allenynes and tosylazide,...
An efficient way to access highly functionalized proline derivatives was developed based on a Cu(I)-catalyzed reaction between CF-substituted allenynes and tosylazide, which involved a cascade of [3 + 2]-cycloaddition/ketenimine and a rearrangement/Alder-ene cyclization to afford the new proline framework with a high diastereoselectivity.
Topics: Proline; Stereoisomerism; Catalysis; Cyclization; Cycloaddition Reaction; Molecular Structure
PubMed: 36296490
DOI: 10.3390/molecules27206898 -
ELife Mar 2022Cellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the...
Cellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that arise during differentiation. Using a bioinformatic approach, we discovered that osteoblast differentiation is associated with increased demand for the amino acid proline. When compared to other differentiated cells, osteoblast-associated proteins, including RUNX2, OSX, OCN, and COL1A1, are significantly enriched in proline. Using a genetic and metabolomic approach, we demonstrate that the neutral amino acid transporter SLC38A2 acts cell-autonomously to provide proline to facilitate the efficient synthesis of proline-rich osteoblast proteins. Genetic ablation of SLC38A2 in osteoblasts limits both osteoblast differentiation and bone formation in mice. Mechanistically, proline is primarily incorporated into nascent protein with little metabolism observed. Collectively, these data highlight a requirement for proline in fulfilling the unique biosynthetic requirements that arise during osteoblast differentiation and bone formation.
Topics: Animals; Cell Differentiation; Mice; Osteoblasts; Osteogenesis; Proline; Proteins
PubMed: 35261338
DOI: 10.7554/eLife.76963 -
Scientific Reports Aug 2022The aim of the present research was to understand the impacts of foliar nitrogen and α-oxoglutarate on proline accumulation, photosynthesis, and ammonium assimilation...
The aim of the present research was to understand the impacts of foliar nitrogen and α-oxoglutarate on proline accumulation, photosynthesis, and ammonium assimilation of soybean seedlings subjected to drought stress. The data in the present study demonstrated that foliar α-oxoglutarate and nitrogen significantly enhanced leaf glutamine synthetase (GS) activity, glutamate dehydrogenase (GDH) activity, glutamate content, proline content, relative water content (RWC) and photosynthesis of soybean seedlings exposed to drought stress at each stage. Accordingly, the ammonium content was significantly reduced by foliar α-oxoglutarate and nitrogen. These results suggested that a combination of foliar nitrogen plus α-oxoglutarate had an advantage over either foliar nitrogen or foliar α-oxoglutarate in increasing the proline accumulation under drought stress and a combination of foliar nitrogen plus α-oxoglutarate could better mitigate the adverse impacts of drought stress.
Topics: Ammonium Compounds; Droughts; Ketoglutaric Acids; Nitrogen; Photosynthesis; Plant Leaves; Proline; Seedlings; Glycine max
PubMed: 36002532
DOI: 10.1038/s41598-022-18660-4