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Physiologia Plantarum Jun 2021Drought stress, which causes a decline in quality and quantity of crop yields, has become more accentuated these days due to climatic change. Serious measures need to be... (Review)
Review
Drought stress, which causes a decline in quality and quantity of crop yields, has become more accentuated these days due to climatic change. Serious measures need to be taken to increase the tolerance of crop plants to acute drought conditions likely to occur due to global warming. Drought stress causes many physiological and biochemical changes in plants, rendering the maintenance of osmotic adjustment highly crucial. The degree of plant resistance to drought varies with plant species and cultivars, phenological stages of the plant, and the duration of plant exposure to the stress. Osmoregulation in plants under low water potential relies on synthesis and accumulation of osmoprotectants or osmolytes such as soluble proteins, sugars, and sugar alcohols, quaternary ammonium compounds, and amino acids, like proline. This review highlights the role of osmolytes in water-stressed plants and of enzymes entailed in their metabolism. It will be useful, especially for researchers working on the development of drought-resistant crops by using the metabolic-engineering techniques.
Topics: Droughts; Osmoregulation; Osmosis; Proline; Stress, Physiological; Water
PubMed: 33280137
DOI: 10.1111/ppl.13297 -
JCI Insight Aug 2023Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1...
Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1 function in allergic asthmatic airway remodeling via EMT has not yet been addressed to our knowledge. In the present study, increased levels of plasma proline and PYCR1 were observed in patients with asthma. Similarly, proline and PYCR1 in lung tissues were high in a murine allergic asthma model induced by house dust mites (HDMs). Pycr1 knockout decreased proline in lung tissues, with reduced airway remodeling and EMT. Mechanistically, loss of Pycr1 restrained HDM-induced EMT by modulating mitochondrial fission, metabolic reprogramming, and the AKT/mTORC1 and WNT3a/β-catenin signaling pathways in airway epithelial cells. Therapeutic inhibition of PYCR1 in wild-type mice disrupted HDM-induced airway inflammation and remodeling. Deprivation of exogenous proline relieved HDM-induced airway remodeling to some extent. Collectively, this study illuminates that proline and PYCR1 involved with airway remodeling in allergic asthma could be viable targets for asthma treatment.
Topics: Animals; Mice; Airway Remodeling; Proline; Asthma; Lung; Hypersensitivity
PubMed: 37432745
DOI: 10.1172/jci.insight.167395 -
Cell Death and Differentiation Aug 2023Solute carrier family 25 member 51 (SLC25A51) was recently identified as the mammalian mitochondrial NAD+ transporter essential for mitochondria functions. However, the...
Solute carrier family 25 member 51 (SLC25A51) was recently identified as the mammalian mitochondrial NAD+ transporter essential for mitochondria functions. However, the role of SLC25A51 in human disease, such as cancer, remains undefined. Here, we report that SLC25A51 is upregulated in multiple cancers, which promotes cancer cells proliferation. Loss of SLC25A51 elevates the mitochondrial proteins acetylation levels due to SIRT3 dysfunctions, leading to the impairment of P5CS enzymatic activity, which is the key enzyme in proline biogenesis, and the reduction in proline contents. Notably, we find fludarabine phosphate, an FDA-approved drug, is able to bind with and inhibit SLC25A51 functions, causing mitochondrial NAD decrease and proteins hyperacetylation, which could further synergize with aspirin to reinforce the anti-tumor efficacy. Our study reveals that SLC25A51 is an attractive anti-cancer target, and provides a novel drug combination of fludarabine phosphate with aspirin as a potential cancer therapy strategy.
Topics: Animals; Humans; Acetylation; Proline; Mitochondria; Sirtuin 3; Homeostasis; Mammals
PubMed: 37419986
DOI: 10.1038/s41418-023-01185-2 -
Trends in Plant Science Jan 2022Proline is a multifunctional amino acid that is accumulated in high concentrations in plants under various stress conditions. Proline accumulation is intimately... (Review)
Review
Proline is a multifunctional amino acid that is accumulated in high concentrations in plants under various stress conditions. Proline accumulation is intimately connected to many cellular processes, such as osmotic pressure, energy status, nutrient availability, changes in redox balance, and defenses against pathogens. Proline biosynthesis and catabolism is linked to photosynthesis and mitochondrial respiration, respectively. Proline can function as a signal, modulating gene expression and certain metabolic processes. We review important findings on proline metabolism and function of the last decade, giving a more informative picture about the function of this unusual amino acid in maintaining cellular homeostasis, modulating plant development, and promoting stress acclimation.
Topics: Osmotic Pressure; Photosynthesis; Plant Development; Plants; Proline
PubMed: 34366236
DOI: 10.1016/j.tplants.2021.07.009 -
The New England Journal of Medicine Sep 2022
Topics: Antiviral Agents; Drug Combinations; Humans; Lactams; Leucine; Nitriles; Proline; Recurrence; Ritonavir; Viral Load; COVID-19 Drug Treatment
PubMed: 36069818
DOI: 10.1056/NEJMc2205944 -
Journal of Wound Care Jan 2021We evaluated the effects of a specialised oral nutritional supplement (ONS) containing arginine and proline, with high vitamin A, C and E, zinc and selenium content, on... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
We evaluated the effects of a specialised oral nutritional supplement (ONS) containing arginine and proline, with high vitamin A, C and E, zinc and selenium content, on the repair of hard-to-heal wounds.
METHOD
Patients with hard-to-heal wounds were evaluated at five timepoints (S0-S4) over four consecutive weeks. At S0 patients were randomised to the specialised ONS (n=15; 25 wounds) or control (n=15; 25 wounds) groups. Posology was 200ml twice daily over the research period. Wound surface area and perimeter were monitored. In addition to the metric data, it was also possible to calculate the rate of wound contraction and the linear growth of the wound edges, looking for wound-healing predictive factors.
RESULTS
A total of 30 patients took part in the study. Mean age was 65 years and 50% of patients had diabetes. Of the total evaluated wounds, 78% were <50cm, 14% were 50-150cm and 8% were >250cm. In 96% of cases, the wounds were in the lower limbs. A statistically significant reduction (p=0.004) in surface area of the wounds due to the specialised ONS, with a performance peak between S1 and S2, was observed. This specialised ONS did not induce changes in blood pressure, blood glucose level or renal function. A mean weekly wound edge growth of 1.85mm in patients with diabetes and 3.0mm in those without diabetes was observed. These results were 2.9 and 4.6 times, respectively, higher than expected, according to the literature.
CONCLUSION
Specialised ONS can be a therapeutic option for hard-to-heal wounds.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Dietary Supplements; Female; Humans; Male; Middle Aged; Pressure Ulcer; Proline; Treatment Outcome; Wound Healing; Zinc
PubMed: 33439085
DOI: 10.12968/jowc.2021.30.1.26 -
The Journal of Organic Chemistry Mar 2021We introduce the efficient Fmoc-SPPS and peptoid synthesis of Q-proline-based, metal-binding macrocycles (QPMs), which bind metal cations and display nine functional...
We introduce the efficient Fmoc-SPPS and peptoid synthesis of Q-proline-based, metal-binding macrocycles (QPMs), which bind metal cations and display nine functional groups. Metal-free QPMs are disordered, evidenced by NMR and a crystal structure of QPM- obtained through racemic crystallization. Upon addition of metal cations, QPMs adopt ordered structures. Notably, the addition of a second functional group at the hydantoin amide position (R) converts the proline ring from Cγ-endo to Cγ-exo, due to steric interactions.
Topics: Crystallization; Magnetic Resonance Spectroscopy; Models, Molecular; Proline
PubMed: 33635647
DOI: 10.1021/acs.joc.1c00116 -
Amino Acids Dec 2021Cancer cells often change their metabolism to support uncontrolled proliferation. Proline is the only proteogenic secondary amino acid that is abundant in the body.... (Review)
Review
Cancer cells often change their metabolism to support uncontrolled proliferation. Proline is the only proteogenic secondary amino acid that is abundant in the body. Recent studies have shown that proline metabolism plays an important role in metabolic reprogramming and affects the occurrence and development of cancer. Proline metabolism is related to ATP production, protein and nucleotide synthesis, and redox homeostasis in tumor cells. Proline can be synthesized by aldehyde dehydrogenase family 18 member A1 (ALDH18A1) and delta1-pyrroline-5-carboxylate reductase (PYCR), up-regulating ALDH18A1 and PYCR can promote the proliferation and invasion of cancer cells. As the main storage of proline, collagen can influence cancer cells proliferation, invasion, and metastasis. Its synthesis depends on the hydroxylation of proline catalyzed by prolyl 4-hydroxylases (P4Hs), which will affect the plasticity and metastasis of cancer cells. The degradation of proline occurs in the mitochondria and involves an oxidation step catalyzed by proline dehydrogenase/proline oxidase (PRODH/POX). Proline catabolism has a dual role in cancer, linking apoptosis with the survival and metastasis of cancer cells. In addition, it has been demonstrated that the regulation of proline metabolic enzymes at the genetic and post-translational levels is related to cancer. This article reviews the role of proline metabolic enzymes in cancer proliferation, apoptosis, metastasis, and development. Research on proline metabolism may provide a new strategy for cancer treatment.
Topics: Animals; Apoptosis; Cell Proliferation; Humans; Neoplasm Metastasis; Neoplasms; Proline
PubMed: 34390414
DOI: 10.1007/s00726-021-03060-1 -
Molecules and Cells Nov 2022Proline plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes. Here, we... (Review)
Review
Proline plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes. Here, we focus our review on proline metabolism in neurons, highlighting the role of dysregulated proline metabolism in neuronal dysfunction and consequently neurological and psychiatric disorders. We will discuss the association between genetic and protein function of enzymes in the proline pathway and the development of neurological and psychiatric disorders. We will conclude with a potential mechanism of proline metabolism in neuronal function and mental health.
Topics: Humans; Mental Disorders; Proline
PubMed: 36324271
DOI: 10.14348/molcells.2022.0115 -
Current Opinion in Biotechnology Dec 2023Proline is a nonessential amino acid, and its metabolism has been implicated in numerous malignancies. Together with a direct role in regulating cancer cells'... (Review)
Review
Proline is a nonessential amino acid, and its metabolism has been implicated in numerous malignancies. Together with a direct role in regulating cancer cells' proliferation and survival, proline metabolism plays active roles in shaping the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) display high rates of proline biosynthesis to support the production of collagen for the extracellular matrix (ECM). Indeed, impaired proline metabolism in CAFs results in reduced collagen deposition and compromises the growth and metastatic spread of cancer. Moreover, the rate of proline metabolism regulates intracellular reactive oxygen species (ROS) levels, which influence the production and release of cytokines from cancer cells, contributing toward an immune-permissive TME. Hence, targeting proline metabolism is a promising anticancer strategy that could improve patients' outcome and response to immunotherapy.
Topics: Humans; Immune Evasion; Neoplasms; Collagen; Extracellular Matrix; Proline; Tumor Microenvironment
PubMed: 37864905
DOI: 10.1016/j.copbio.2023.103011