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Plants (Basel, Switzerland) May 2024Hairgrass (), a widely distributed grass species considered promising in the ecological restoration of degraded grassland in the Qinghai-Xizang Plateau, is likely to be...
Hairgrass (), a widely distributed grass species considered promising in the ecological restoration of degraded grassland in the Qinghai-Xizang Plateau, is likely to be subjected to frequent drought and waterlogging stress due to ongoing climate change, further aggravating the degradation of grassland in this region. However, whether it would acclimate to water stresses resulting from extreme climates remains unknown. Proline accumulation is a crucial metabolic response of plants to challenging environmental conditions. This study aims to investigate the changes in proline accumulation and key enzymes in hairgrass shoot and root tissues in response to distinct climate extremes including moderate drought, moderate waterlogging, and dry-wet variations over 28 days using a completely randomized block design. The proline accumulation, contribution of the glutamate and ornithine pathways, and key enzyme activities related to proline metabolism in shoot and root tissues were examined. The results showed that water stress led to proline accumulation in both shoot and root tissues of hairgrass, highlighting the importance of this osmoprotectant in mitigating the effects of environmental challenges. The differential accumulation of proline in shoots compared to roots suggests a strategic allocation of resources by the plant to cope with osmotic stress. Enzymatic activities related to proline metabolism, such as Δ-pyrroline-5-carboxylate synthetase, ornithine aminotransferase, Δ-pyrroline-5-carboxylate reductase, Δ-pyrroline-5-carboxylate dehydrogenase, and proline dehydrogenase, further emphasize the dynamic regulation of proline levels in hairgrass under water stress conditions. These findings support the potential for enhancing the stress resistance of hairgrass through the genetic manipulation of proline biosynthesis and catabolism pathways.
PubMed: 38794479
DOI: 10.3390/plants13101408 -
Scientific Reports Sep 2023Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that ranks first in morbidity and mortality. Abnormal arginine metabolism is associated with inflammatory...
Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that ranks first in morbidity and mortality. Abnormal arginine metabolism is associated with inflammatory lung disease and may influence alterations in the tumor immune microenvironment. However, the potential role of arginine and proline metabolic patterns and immune molecular markers in LUAD is unclear. Gene expression, somatic mutations, and clinicopathological information of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was performed to identify metabolic genes associated with overall survival (OS). Unsupervised clustering divided the sample into two subtypes with different metabolic and immunological profiles. Gene set enrichment analysis (GESA) and gene set variation analysis (GSVA) were used to analyze the underlying biological processes of the two subtypes. Drug sensitivity between subtypes was also predicted; then prognostic features were developed by multivariate Cox regression analysis. In addition, validation was obtained in the GSE68465, and GSE50081 dataset. Then, gene expression, and clinical characterization of hub genes CPS1 and SMS were performed; finally, in vitro validation experiments for knockdown of SMS were performed in LUAD cell lines. In this study, we first identified 12 arginine and proline-related genes (APRGs) significantly associated with OS and characterized the clinicopathological features and tumor microenvironmental landscape of two different subtypes. Then, we established an arginine and proline metabolism-related scoring system and identified two hub genes highly associated with prognosis, namely CPS1, and SMS. In addition, we performed CCK8, transwell, and other functional experiments on SMS to obtain consistent results. Our comprehensive analysis revealed the potential molecular features and clinical applications of APRGs in LUAD. A model based on 2 APRGs can accurately predict survival outcomes in LUAD, improve our understanding of APRGs in LUAD, and pave a new pathway to guide risk stratification and treatment strategy development for LUAD patients.
Topics: Humans; Prognosis; Adenocarcinoma of Lung; Arginine; Cell Line; Lung Neoplasms; Tumor Microenvironment
PubMed: 37709932
DOI: 10.1038/s41598-023-42541-z -
Cancer Science Jul 2023FK506 binding protein 52 (FKBP52) (gene name FKBP4) is a 52 kDa protein that belongs to the FKBP family; it binds to the immunosuppressant FK506 and has proline... (Review)
Review
FK506 binding protein 52 (FKBP52) (gene name FKBP4) is a 52 kDa protein that belongs to the FKBP family; it binds to the immunosuppressant FK506 and has proline isomerase activity. In addition to its FK domain-containing peptidylprolyl isomerase activity, FKBP52 also acts as a cochaperone through the tetratricopeptide repeat domain that mediates binding to heat shock protein 90. Previous studies have reported that FKBP52 is associated with hormone-dependent, stress-related, and neurodegenerative diseases, revealing its diverse functions. In particular, the effects of FKBP52 on cancer have attracted considerable attention. FKBP52 promotes the growth of hormone-dependent cancers by activating steroid hormone receptors. Recent studies have shown that the expression of FKBP52 is increased not only in steroid hormone-dependent cancer cells but also in colorectal, lung, and liver cancers, revealing its diverse functions that contribute to cancer growth. This review summarizes reports related to hormone-dependent cancer and cell proliferation in terms of the structure of FKBP52 and its function on interacting molecules.
Topics: Humans; Cell Proliferation; HSP90 Heat-Shock Proteins; Neoplasms, Hormone-Dependent; Protein Binding; Tacrolimus Binding Proteins
PubMed: 37026526
DOI: 10.1111/cas.15811 -
The Journal of Biological Chemistry Nov 2023Neurodegenerative tauopathies are caused by the transition of tau protein from a monomer to a toxic aggregate. They include Alzheimer disease (AD), progressive...
Neurodegenerative tauopathies are caused by the transition of tau protein from a monomer to a toxic aggregate. They include Alzheimer disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick disease (PiD). We have previously proposed that tau monomer exists in two conformational ensembles: an inert form (M), which does not self-assemble, and seed-competent form (M), which self-assembles and templates ordered assembly growth. We proposed that cis/trans isomerization of tau at P301, the site of dominant disease-associated S/L missense mutations, might underlie the transition of wild-type tau to a seed-competent state. Consequently, we created monoclonal antibodies using non-natural antigens consisting of fluorinated proline (P∗) at the analogous P270 in repeat 1 (R1), biased toward the trans-configuration at either the R1/R2 (TENLKHQP∗GGGKVQIINKK) or the R1/R3 (TENLKHQP∗GGGKVQIVYK) interfaces. Two antibodies, MD2.2 and MD3.1, efficiently immunoprecipitated soluble seeds from AD and PSP but not CBD or PiD brain samples. The antibodies efficiently stained brain samples of AD, PSP, and PiD, but not CBD. They did not immunoprecipitate or immunostain tau from the control brain. Creation of potent anti-seed antibodies based on the trans-proline epitope implicates local unfolding around P301 in pathogenesis. MD2.2 and MD3.1 may also be useful for therapy and diagnosis.
Topics: Humans; Alzheimer Disease; Antibodies, Monoclonal; Brain; Epitopes; Pick Disease of the Brain; Proline; tau Proteins; Tauopathies
PubMed: 37714465
DOI: 10.1016/j.jbc.2023.105252 -
Journal of Advanced Research Jan 2024Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical...
The circUbqln1, regulated by XBP1s, interplays with 14-3-3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism.
INTRODUCTION
Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention in OA and related drug development due to their unique RNA sequence characteristics.Therefore,exploring the role of cirRNAs in the occurrence and development of OA is of paramount importance for the development of effective medications for OA.
OBJECTIVES
To identify a novel circRNA, circUbqln1, for treating osteoarthritis and elucidate its pathophysiological role and mechanisms in the treatment of OA.
METHODS
The circUbqln1 expression and distribution were determined by qRT-PCR and FISH. XBP1 gene knockout(XBP1 cKO) spontaneous OA and DMM model and WT mouse CIOA model were used to explore the role of XBP1 and circUbqln1 in OA.Overexpression or knockdown of circUbqln1 lentivirus was used to observe the impacts of circUbqln1 on primary chondrocytes,C28/I2 and mice in vitro and in vivo.Chromatin immunoprecipitation,luciferase reporter assay,RNA pulldown,mass spectrometry,RNA immunoprecipitation,fluorescence in situ hybridization,and flow cytometry to explore the molecular mechanisms of circUbqln1.
RESULTS
It was found that cartilage-specific XBP1 cKO mice exhibited a faster OA progression compared to normal's.Importantly,transcript factor XBP1s has the capacity to impede the biogenesis of circUbqln1,derived from Ubqln1. The circUbqln1 promotes cartilage catabolism and inhibits anabolism, therefore accelerates the occurrence of OA.Mechanismly,circUbqln1 can translocate to the chondrocyte nucleus with the assistance of phosphorylated 14-3-3ζ, upregulate the transcriptional activity of the proline dehydrogenase(Prodh) promoter and PRODH enzyme activity. Consequently, this leads to the promotion of proline degradation and the inhibition of collagen synthesis,ultimately culminating in the impairment of cartilage and its structural integrity.
CONCLUSION
CircUbqln1 plays a crucial role in the occurrence and development of OA, indicating that the inhibition of circUbqln1 holds promise as a significant approach for treating OA in the future.
PubMed: 38219870
DOI: 10.1016/j.jare.2024.01.007 -
PeerJ 2023Maize is one of the major crops in the world and the most productive member of the family. Since cold stress affects the germination, growth, and productivity of corn...
Maize is one of the major crops in the world and the most productive member of the family. Since cold stress affects the germination, growth, and productivity of corn seeds, the present study aimed to investigate the effect of seed biopriming with on the tolerance of two genotypes of maize seedlings to cold stress. This study was conducted in triplicates in factorial experiment with a complete randomized block design (CRBD). The study was conducted in the greenhouse and laboratory of the University of Mohaghegh Ardabili, Ardabil, Iran. Experimental factors include two cultivars (AR68 cold-resistant and KSC703 cold-sensitive maize cultivars), four pretreatment levels (control, biopriming with , exogenous and hydropriming), and two levels of cold stress (control and cold at 5 °C) in a hydroponic culture medium. The present study showed that maize leaves' establishment rate and maximum fluorescence (Fm) are affected by triple effects (C*, P*, S). The highest establishment (99.66%) and Fm (994 units) rates were observed in the KP3 control treatment. Moreover, among the pretreatments, the highest (0.476 days) and the lowest (0.182 days) establishment rates were related to P0 and P3 treatments, respectively. Cultivar A showed higher chlorophyll a and b, carotenoid content, and establishment rate compared to cultivar K in both optimal and cold conditions. The highest root dry weight (11.84 units) was obtained in cultivar A with P3 pretreatment. The pretreatments with increased physiological parameters and seedling emergence of maize under cold and optimal stress conditions. Pretreatment and cultivar improved catalase activity in roots and leaves. Higher leaf and root catalase activity was observed in the roots and leaves of cultivar K compared to cultivar A. The cold treatment significantly differed in peroxidase activity from the control treatment. Cultivar K showed higher catalase activity than cultivar A. The main effects of pretreatment and cold on polyphenol oxidase activity and proline content showed the highest polyphenol oxidase activity and proline content in hydropriming (H) treatment. Cold treatment also showed higher polyphenol oxidase activity and proline content than cold-free conditions.
Topics: Zea mays; Cold-Shock Response; Catalase; Chlorophyll A; Catechol Oxidase
PubMed: 37645014
DOI: 10.7717/peerj.15644 -
BioRxiv : the Preprint Server For... Jan 2024Antimicrobial peptides (AMPs) are essential elements of natural cellular combat and candidates as antibiotic therapy. Elevated function may be needed for robust...
Antimicrobial peptides (AMPs) are essential elements of natural cellular combat and candidates as antibiotic therapy. Elevated function may be needed for robust physiological performance. Yet, both pure protein design and combinatorial library discovery are hindered by the complexity of antimicrobial activity. We applied a recently developed high-throughput technique, sequence-activity mapping of AMPs via depletion (SAMP-Dep), to proline-rich AMPs. Robust self-inhibition was achieved for metalnikowin 1 (Met) and apidaecin 1b (Api). SAMP-Dep exhibited high reproducibility with correlation coefficients 0.90 and 0.92, for Met and Api, respectively, between replicates and 0.99 and 0.96 for synonymous genetic variants. Sequence-activity maps were obtained via characterization of 26,000 and 34,000 mutants of Met and Api, respectively. Both AMPs exhibit similar mutational profiles including beneficial mutations at one terminus, the C-terminus for Met and N-terminus for Api, which is consistent with their opposite binding orientations in the ribosome. While Met and Api reside with the family of proline-rich AMPs, different proline sites exhibit substantially different mutational tolerance. Within the PRP motif, proline mutation eliminates activity, whereas non-PRP prolines readily tolerate mutation. Homologous mutations are more tolerated, particularly at alternating sites on one 'face' of the peptide. Important and consistent epistasis was observed following the PRP domain within the segment that extends into the ribosomal exit tunnel for both peptides. Variants identified from the SAMP-Dep platform were produced and exposed toward Gram-negative species exogenously, showing either increased potency or specificity for strains tested. In addition to mapping sequence-activity space for fundamental insight and therapeutic engineering, the results advance the robustness of the SAMP-Dep platform for activity characterization.
PubMed: 38352424
DOI: 10.1101/2024.01.28.577586 -
BMC Cancer Dec 2023Prostate cancer is a common solid tumor that affects a significant number of men worldwide. Conventional androgen deprivation therapy (ADT) increases the risk of...
BACKGROUND
Prostate cancer is a common solid tumor that affects a significant number of men worldwide. Conventional androgen deprivation therapy (ADT) increases the risk of developing castration-resistant prostate cancer (CRPC). Effective clinical management of patients with CRPC is challenging due to the limited understanding.
METHODS
In this study, transcriptomic and metabolomic profiles of androgen-dependent prostate cancer cell line LNCaP and the androgen-independent cells developed from LNCaP cells (LNCaP-ADR) were investigated using RNA-sequencing and LC-MS/MS, respectively. The differentially expressed genes and metabolites were analyzed, and integrative analysis of transcriptomic and metabolomic data was further conducted to obtain a comprehensive understanding of the metabolic characteristics in LNCaP-ADR cells. Quantitative real-time PCR (QPCR) was employed to ascertain the mRNA expression levels of the selected differentially expressed genes.
RESULTS
The arginine and proline metabolism pathway was identified as a commonly altered pathway at both the transcriptional and metabolic levels. In the LNCaP-ADR cells, significant upregulation was observed for metabolites including 5-Aminopentanoic acid, L-Arginine, L-Glutamic acid, N-Acetyl-L-alanine, and Pyrrole-2-carboxylic acid at the metabolic level. At the transcriptional level, MAOA, ALDH3A2, ALDH2, ARG1, CKMT2, and CNDP1 were found to be significantly upregulated in the LNCaP-ADR cells. Gene set enrichment analysis (GSEA) identified various enriched gene sets in the LNCaP-ADR cells, encompassing inflammatory response, 9plus2 motile cilium, motile cilium, ciliary plasm, cilium or flagellum-dependent cell motility, cilium movement, cilium, response to endoplasmic reticulum stress, PTEN DN.V1 DN, SRC UP.V1 UP, IL15 UP.V1 DN, RB DN.V1 DN, AKT UP MTOR DN.V1 UP, VEGF A UP.V1 UP, and KRAS.LUNG.BREAST UP.V1 UP.
CONCLUSIONS
These findings highlight the substantial association between the arginine and proline metabolism pathway and CRPC, emphasizing the need to prioritize strategies that target dysregulated metabolites and differentially expressed genes as essential interventions in the clinical management of CRPC.
Topics: Male; Humans; Prostatic Neoplasms; Androgens; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists; Chromatography, Liquid; Tandem Mass Spectrometry; Gene Expression Profiling; Transcriptome; Arginine; Proline; Cell Line, Tumor; Receptors, Androgen; Gene Expression Regulation, Neoplastic; Aldehyde Dehydrogenase, Mitochondrial
PubMed: 38104097
DOI: 10.1186/s12885-023-11707-3 -
BMC Plant Biology Apr 2024Salinity stress ranks among the most prevalent stress globally, contributing to soil deterioration. Its negative impacts on crop productivity stem from mechanisms such...
Salinity stress ranks among the most prevalent stress globally, contributing to soil deterioration. Its negative impacts on crop productivity stem from mechanisms such as osmotic stress, ion toxicity, and oxidative stress, all of which impede plant growth and yield. The effect of cobalt with proline on mitigating salinity impact in radish plants is still unclear. That's why the current study was conducted with aim to explore the impact of different levels of Co and proline on radish cultivated in salt affected soils. There were four levels of cobalt, i.e., (0, 10, 15 and 20 mg/L) applied as CoSO and two levels of proline (0 and 0.25 mM), which were applied as foliar. The treatments were applied in a complete randomized design (CRD) with three replications. Results showed that 20 CoSO with proline showed improvement in shoot length (∼ 20%), root length (∼ 23%), plant dry weight (∼ 19%), and plant fresh weight (∼ 41%) compared to control. The significant increase in chlorophyll, physiological and biochemical attributes of radish plants compared to the control confirms the efficacy of 20 CoSO in conjunction with 10 mg/L proline for mitigating salinity stress. In conclusion, application of cobalt with proline can help to alleviate salinity stress in radish plants. However, multiple location experiments with various levels of cobalt and proline still needs in-depth investigations to validate the current findings.
Topics: Antioxidants; Proline; Raphanus; Cobalt; Salt Stress; Salinity
PubMed: 38627664
DOI: 10.1186/s12870-024-04998-6 -
Human Reproduction (Oxford, England) Nov 2023Is the abundance of certain biochemical compounds in human cumulus cells (CCs) related to oocyte quality?
STUDY QUESTION
Is the abundance of certain biochemical compounds in human cumulus cells (CCs) related to oocyte quality?
SUMMARY ANSWER
Malonate, 5-oxyproline, and erythronate were positively associated with pregnancy potential.
WHAT IS KNOWN ALREADY
CCs are removed and discarded prior to ICSI, thereby constituting an interesting biological material on which to perform molecular analysis aimed to predict oocyte developmental competence. Mitochondrial DNA content and transcriptional analyses in CC have been shown to provide a poor predictive value of oocyte competence, but the untargeted analysis of biochemical compounds (metabolomics) has been unexplored.
STUDY DESIGN, SIZE, DURATION
CCs were obtained from three groups of cumulus-oocyte complexes (COCs) of known developmental potential: oocytes not developing to blastocyst following ICSI (Bl-); oocytes developing to blastocyst but failing to establish pregnancy following embryo transfer (P-); and oocytes developing to blastocyst able to establish a pregnancy (P+). Metabolomics analyses were performed on 12 samples per group, each sample comprising the CC recovered from a single COC.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Human CC samples were obtained from IVF treatments. Only unfrozen oocytes and embryos not submitted to preimplantation genetic testing were included in the analysis. Metabolomics analysis was performed by ultra-high performance liquid chromatography-tandem mass spectroscopy.
MAIN RESULTS AND THE ROLE OF CHANCE
The analysis identified 98 compounds, five of which were differentially abundant (P < 0.05) between groups: asparagine, proline, and malonate were less abundant in P- compared to Bl-, malonate and 5-oxoproline were less abundant in P- group compared to P+, and erythronate was less abundant in Bl- group compared to P+. No significant association between the abundance of the compounds identified and donor age or BMI was noted.
LIMITATIONS, REASONS FOR CAUTION
Data dispersion and the lack of coherence between developmental groups preclude the direct use of metabolic markers in clinical practice, where the uterine environment plays a major role in pregnancy outcome. The abundance of other compounds not detected by the analysis may be associated with oocyte competence. As donors were lean (only two with BMI > 30 kg/m2) and young (<34 years old), a possible effect of obesity or advanced age on the CC metabolome could not be determined.
WIDER IMPLICATIONS OF THE FINDINGS
The abundance of malonate, 5-oxyproline, and erythronate in CC was significantly higher in COCs ultimately establishing pregnancy, providing clues on the pathways required for oocyte competence. The untargeted analysis uncovered the presence of compounds that were not expected in CC, such as β-citrylglutamate and the neurotransmitter N-acetyl-aspartyl-glutamate, which may play roles in chromatin remodeling and signaling, respectively.
STUDY FUNDING/COMPETING INTEREST(S)
Research was supported by the Industrial Doctorate Project IND2017/BIO-7748 funded by Madrid Region Government. The authors declare no competing interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Female; Humans; Pregnancy; Adult; Cumulus Cells; Hydroxyproline; Oocytes; Oogenesis; Malonates
PubMed: 37697661
DOI: 10.1093/humrep/dead181