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1.
Food Chem ; 401: 134195, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36116301

RESUMO

Soybean peptides were reported to promote the growth and metabolism of Lacticaseibacillus rhamnosus (L. rhamnosus) Lra05. However, the relationship between L. rhamnosus Lra05 and the characteristics of soybean peptides is still unclear. Therefore, digested soybean peptides (dPEP) after 36 h utilization by L. rhamnosus Lra05 were identified and analyzed. We found that L. rhamnosus Lra05 tends to utilize hydrophobic peptides with three to five amino acids residues, and hydrophilic peptides with more than five residues. They also prefer peptides with proline at penultimate C-terminal position or arginine at ultimate C-terminal position. Moreover, fraction 1 (F1) and fraction 7 (F7) acquired from dPEP using RP-HPLC exhibited the strongest growth and metabolism promoting effects, and the utilized characteristics of F1 and F7 were similar with those of dPEP. These results explained why soybean peptides could promote L. rhamnosus to some extent and strengthen theoretical basis for the application of soybean peptides as potential prebiotics.


Assuntos
Lactobacillus rhamnosus , Soja , Soja/metabolismo , Peptídeos/química , Aminoácidos/metabolismo , Prolina/metabolismo , Arginina/metabolismo
2.
Gene ; 850: 146955, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36220447

RESUMO

The present research aims to evaluate the effect of swimming exercise and chitosan-coated l-arginine on mitochondrial oxidation, BCL2 Interacting Protein 3 (Bnip3), NIP-like protein × (Nix), B-cell lymphoma-extra-large (Bcl-xL) and autophagy-related protein light chain 3(LC3) expression in soleus muscle of aging rats. In this experimental research, 25 male Wistar rats were assigned into five groups randomly: young, old, old + Nano l-arginine (Nano L-a), old + exercise (Ex), and old + Nano l-arginine (Nano L-a) + exercise (Ex) (n = 5 in each). They performed a swimming exercise program five days a week for six weeks. To determine the relative strength for rats before and after performing these interventions, the 1repetition maximum (1RM) test was done as a pre and post-test. The exercise program started with 20 min and after four sessions, gradually increased to 60 min and this time was maintained until the completion of the training period. l-arginine coated with chitosan nanoparticles was given to the rats in the l-arginine-supplemented group via gavage at a dosage of 500 mg/kg/day, five days a week, for six weeks. Additionally, the rats in all groups were fed a normal diet (2.87 kcal/g and 15 % energy from fat). Upon the completion of the protocol implementation, the rats were sacrificed and the soleus muscle was fixed and frozen to determine hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), gene expression analysis, levels of reactive oxygen species (ROS), and total antioxidant capacity (TAC). The results from the present research indicated that swimming exercise and Nano l-arginine improve the strength and histology of muscle tissue in old rats (p < 0.05). Aging significantly increased the expression of Nix and Bnip3 (p < 0.05) and reduced the Bcl-xL gene expression (p < 0.05). The expression of LC3 protein also increased with aging (p < 0.05). Therapeutic interventions, such as combined treatment (old + Nano L-a + Ex) for old animals, reduced the amount of this protein in soleus muscle (p < 0.05). The ROS values also showed a significant reduction only in the old + Nano L-a + Ex group compared to the old group. Moreover, TAC values show a significant decrease in the old and old + Ex groups in comparison to the young group. The use of arginine supplement, especially in nano form, along with swimming exercise seems to reduce the oxidative damage to the elderly muscle tissue, which has a positive effect on the structure and function of the soleus muscle. Since these interventions only had a significant effect on LC3 protein, further studies with more diverse measurement methods for autophagy are suggested.


Assuntos
Quitosana , Condicionamento Físico Animal , Animais , Masculino , Ratos , Envelhecimento/metabolismo , Antioxidantes/farmacologia , Arginina/farmacologia , Arginina/metabolismo , Autofagia , Proteínas Relacionadas à Autofagia/metabolismo , Quitosana/farmacologia , Suplementos Nutricionais , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Músculo Esquelético/metabolismo , Estresse Oxidativo , Condicionamento Físico Animal/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Natação
3.
J Steroid Biochem Mol Biol ; 225: 106180, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36243205

RESUMO

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) mainly degrades asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor. Emerging evidence suggested that plasma ADMA is accumulated in patients with polycystic ovary syndrome (PCOS). However, ADMA-DDAH1 involvement in PCOS pathogenesis is unclear. Here, we used dehydroepiandrosterone (DHEA)-induced PCOS rats and the ovarian granulosa cell line KGN to investigate the effect of the ADMA-DDAH1 pathway on ovarian apoptosis. Moreover, we also quantified the ADMA levels and redox status in human serum specimens, Sprague Dawley rats and KGN cells to investigate the effect of ADMA-DDAH1 on redox status and ovarian apoptosis in PCOS. We enrolled 19 women with PCOS and 17 healthy women (controls) in this study. The women with PCOS had increased serum ADMA levels and decreased glutathione peroxidase (GSH-PX) compared with the controls. In Sprague Dawley rats, 21-day DHEA treatment established PCOS and the rat contained higher ADMA levels in serum and lower DDAH1 expression in ovaries. Moreover, the PCOS rat serum and ovaries exhibited increased levels of the oxidative stress marker malondialdehyde (MDA). ADMA treatment of the KGN cells induced reactive oxygen species accumulation and led to apoptosis. Contrastingly, overexpressing DDAH1 in the KGN cells significantly decreased ADMA levels, enhanced cell viability, and inhibited oxidative stress, while the effect was inverse in DDAH1 knockdown cells. Overall, our results demonstrated that PCOS involves elevated ADMA levels and redox imbalance. The ADMA-DDAH1 pathway exerted a marked effect on oxidative stress and ovarian apoptosis in PCOS. Our findings suggested that strategies for increasing DDAH1 activity in ovarian cells may provide a novel approach for ameliorating PCOS.


Assuntos
Síndrome do Ovário Policístico , Humanos , Feminino , Ratos , Animais , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Ratos Sprague-Dawley , Amidoidrolases/genética , Amidoidrolases/metabolismo , Transdução de Sinais , Arginina/metabolismo , Apoptose , Desidroepiandrosterona/farmacologia
4.
Behav Brain Res ; 437: 114103, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36089098

RESUMO

Mephedrone, a popular psychostimulating substance widely used illegally in recreational purposes, exerts in rodents that regularly and intermittently were exposed to it a sensitized response to the drug. Behavioral sensitization is one of experimental models of drug dependency/abuse liability. In the present study we evaluated a potential involvement of the L-arginine-NO-cGMP pathway in the development of sensitization to the mephedrone-induced hyperlocomotion. Locomotor activity was measured automatically and experiments were performed on male Albino Swiss mice. We demonstrated that a 5-day administration of 7-nitroindazole (10 or 20 mg/kg/day) and L-NAME (50 mg/kg/day) suppressed the development of sensitization to the mephedrone-induced hyperlocomotion. As for L-arginine (125 or 250 mg/kg/day) and methylene blue (5 or 10 mg/kg/day) the obtained outcomes are inconclusive. Furthermore, the lower dose of L-NAME (25 mg/kg/day) surprisingly potentiated the development of sensitization to the mephedrone-induced effects on the spontaneous locomotor activity in mice. In conclusion, our data demonstrated that modulators of the L-arginine-NO-cGMP pathway may differently affect the development of sensitization to the locomotor stimulant effects of mephedrone. Inhibition of neuronal nitric oxide synthase (NOS) seems to prevent this process quite profoundly, non-selective inhibition of NOS may have a dual effect, whereas inhibition of soluble guanylate cyclase may only partially suppress the development of sensitization to the mephedrone-induced effects.


Assuntos
GMP Cíclico , Óxido Nítrico , Animais , Camundongos , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , GMP Cíclico/metabolismo , Arginina/farmacologia , Arginina/metabolismo , Locomoção , Relação Dose-Resposta a Droga
5.
J Inorg Biochem ; 238: 112035, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36327499

RESUMO

Nitric oxide synthase (NOS) is a cytochrome P450-type mono­oxygenase that catalyzes the oxidation of L-arginine to nitric oxide. We previously observed that intramolecular electron transfer from biopterin to Fe2+-O2 in Deinococcus radiodurans NOS (DrNOS) using pulse radiolysis. However, the rate of electron transfer in DrNOS (2.2 × 103 s-1) contrasts with a reported corresponding rate (11 s-1) in a mammalian NOS determined using rapid freeze-quench (RFQ) EPR. We applied pulse radiolysis to Bacillus subtilis NOS (bsNOS) and to rat neural NOS oxygenase domain NOS (mNOS). Concurrently, RFQ EPR was used to trap a pterin radical during single-turnover enzyme reactions of the enzymes. By using the pulse radiolysis method, hydrated electrons (eaq-) reduced the heme iron of NOS enzymes. Subsequently, ferrous heme reacted with O2 to form a Fe2+-O2 intermediate. In the presence of pterin, the intermediate of bsNOS was found to convert to other intermediate in the time range of milliseconds. A similar process was determined to have occurred after pulse radiolysis of the pterin-bound mNOS, though the rate was much slower. The intermediates of all of the NOS enzymes further converted to the original ferric form in the time range of seconds. When using the RFQ method, pterin radicals were formed very rapidly in both DrNOS and bsNOS in the time range of milliseconds. In contrast, the pterin radical in mNOS was observed to form slowly, at a rate of ∼20 s-1.


Assuntos
Biopterina , Óxido Nítrico , Ratos , Animais , Biopterina/metabolismo , Óxido Nítrico/metabolismo , Elétrons , Óxido Nítrico Sintase/metabolismo , Heme/metabolismo , Oxirredução , Arginina/metabolismo , Pterinas , Ferro , Compostos Ferrosos , Óxido Nítrico Sintase Tipo II , Mamíferos/metabolismo
6.
Oxid Med Cell Longev ; 2022: 2419412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338341

RESUMO

Arginase is a ubiquitous enzyme in the urea cycle (UC) that hydrolyzes L-arginine to urea and L-ornithine. Two mammalian arginase isoforms, arginase1 (ARG1) and arginase2 (ARG2), play a vital role in the regulation of ß-cell functions, insulin resistance (IR), and vascular complications via modulating L-arginine metabolism, nitric oxide (NO) production, and inflammatory responses as well as oxidative stress. Basic and clinical studies reveal that abnormal alterations of arginase expression and activity are strongly associated with the onset and development of diabetes mellitus (DM) and its complications. As a result, targeting arginase may be a novel and promising approach for DM treatment. An increasing number of arginase inhibitors, including chemical and natural inhibitors, have been developed and shown to protect against the development of DM and its complications. In this review, we discuss the fundamental features of arginase. Next, the regulatory roles and underlying mechanisms of arginase in the pathogenesis and progression of DM and its complications are explored. Furthermore, we review the development and discuss the challenges of arginase inhibitors in treating DM and its related pathologies.


Assuntos
Arginase , Diabetes Mellitus , Animais , Humanos , Arginase/metabolismo , Arginina/metabolismo , Óxido Nítrico/metabolismo , Ureia , Diabetes Mellitus/tratamento farmacológico , Mamíferos/metabolismo
7.
Clin Transl Med ; 12(11): e1113, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394206

RESUMO

BACKGROUND: Dysregulation of alternative splicing (AS) induced by serine/arginine-rich proteins has recently been linked to cancer metastasis. Nonetheless, as a member of the serine/arginine-rich protein family, the involvement of SRSF11 in colorectal cancer (CRC) is unknown. METHODS: The TCGA dataset and clinical samples were used to assess SRSF11 expression levels in CRC. For SRSF11, functional experiments were conducted both in vitro and in vivo. RNA-seq technology was used to analyze and screen SRSF11-triggered AS events, which were then confirmed by in vivo UV crosslinking and immunoprecipitation (CLIP) and mini-gene reporter assays. Jalview software was used to determine the preferential binding motif with relation to exon skipping (ES) events. Furthermore, coimmunoprecipitation (Co-IP) and Phospho-tag SDS-PAGE experiments were used to investigate PAK5-mediated phosphorylation regulation on SRSF11, and in vitro kinase experiments validated the interaction. RESULTS: In CRC, SRSF11 was discovered to be overexpressed and associated with a poor prognosis. And SRSF11 played a pro-metastatic role in vitro and in vivo. By screening SRSF11-regulated AS events, we identified the binding motif of SRSF11-triggered splicing-switching of HSPA12A AS, which specifically regulated HSPA12A AS by directly binding to a motif in exon 2. Mechanistically, the HSPA12A transcript with exon 2 retention increased N-cadherin expression by promoting RNA stability. Furthermore, the oncogenic kinase PAK5 phosphorylated SRSF11 at serine 287, protecting it from ubiquitination degradation. CONCLUSIONS: SRSF11 exerts pro-metastatic effects in CRC by inhibiting the AS of HSPA12A pre-RNA. Our findings point to SRSF11-regulated HSPA12A splicing as a novel relationship between SRSF11-regulated splicing and CRC metastasis and suggest a PAK5/SRSF11/HSPA12A axis as a potential therapeutic target and prognostic biomarker in CRC.


Assuntos
Processamento Alternativo , Neoplasias Colorretais , Humanos , Processamento Alternativo/genética , Arginina/genética , Arginina/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , RNA/metabolismo , Serina/genética , Serina/metabolismo
8.
Int J Mol Sci ; 23(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36361583

RESUMO

Histone methylation, as one of the important epigenetic regulatory mechanisms, plays a significant role in growth and developmental processes and stress responses of plants, via altering the methylation status or ratio of arginine and lysine residues of histone tails, which can affect the regulation of gene expression. Protein arginine methyltransferases (PRMTs) have been revealed to be responsible for histone methylation of specific arginine residues in plants, which is important for maintaining pleiotropic development and adaptation to abiotic stresses in plants. Here, for the first time, a total of eight PRMT genes in maize have been identified and characterized in this study, named as ZmPRMT1-8. According to comparative analyses of phylogenetic relationship and structural characteristics among PRMT gene family members from several representative species, all maize 8 PRMT proteins were categorized into three distinct subfamilies. Further, schematic structure and chromosome location analyses displayed evolutionarily conserved structure features and an unevenly distribution on maize chromosomes of ZmPRMT genes, respectively. The expression patterns of ZmPRMT genes in different tissues and under various abiotic stresses (heat, drought, and salt) were determined. The expression patterns of ZmPRMT genes indicated that they play a role in regulating growth and development and responses to abiotic stress. Eventually, to verify the biological roles of ZmPRMT genes, the transgenic Arabidopsis plants overexpressing ZmPRMT1 gene was constructed as a typical representative. The results demonstrated that overexpression of ZmPRMT1 can promote earlier flowering time and confer enhanced heat tolerance in transgenic Arabidopsis. Taken together, our results are the first to report the roles of ZmPRMT1 gene in regulating flowering time and resisting heat stress response in plants and will provide a vital theoretical basis for further unraveling the functional roles and epigenetic regulatory mechanism of ZmPRMT genes in maize growth, development and responses to abiotic stresses.


Assuntos
Arabidopsis , Arabidopsis/metabolismo , Zea mays/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Histonas/genética , Histonas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/genética , Arginina/metabolismo
9.
Int J Mol Sci ; 23(21)2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36362379

RESUMO

Acute pancreatitis (AP) is a major, globally increasing gastrointestinal disease and a biliary origin is the most common cause. However, the effects of bile acids (BAs), given systemically, on the pancreas and on disease severity remains elusive. In this study, we have investigated the roles of different circulating BAs in animal models for AP to elucidate their impact on disease severity and the underlying pathomechanisms. BAs were incubated on isolated acini and AP was induced through repetitive injections of caerulein or L-arginine; pancreatic duct ligation (PDL); or combined biliopancreatic duct ligation (BPDL). Disease severity was assessed using biochemical and histological parameters. Serum cholecystokinin (CCK) concentrations were determined via enzyme immunoassay. The binding of the CCK1 receptor was measured using fluorescence-labeled CCK. In isolated acini, hydrophobic BAs mitigated the damaging effects of CCK. The same BAs further enhanced pancreatitis in L-arginine- and PDL-based pancreatitis, whereas they ameliorated pancreatic damage in the caerulein and BPDL models. Mechanistically, the binding affinity of the CCK1 receptor was significantly reduced by hydrophobic BAs. The hydrophobicity of BAs and the involvement of CCK seem to be relevant in the course of AP. Systemic BAs may affect the severity of AP by interfering with the CCK1 receptor.


Assuntos
Pancreatite , Camundongos , Animais , Pancreatite/patologia , Ceruletídeo/farmacologia , Ácidos e Sais Biliares/metabolismo , Doença Aguda , Colecistocinina/metabolismo , Modelos Animais de Doenças , Pâncreas/metabolismo , Arginina/farmacologia , Arginina/metabolismo , Interações Hidrofóbicas e Hidrofílicas
10.
J Am Chem Soc ; 144(45): 20582-20589, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36318515

RESUMO

We describe the development and optimization of a methodology to prepare peptides and proteins modified on the arginine residue with an adenosine-di-phosphate-ribosyl (ADPr) group. Our method comprises reacting an ornithine containing polypeptide on-resin with an α-linked anomeric isothiourea N-riboside, ensuing installment of a phosphomonoester at the 5'-hydroxyl of the ribosyl moiety followed by the conversion into the adenosine diphosphate. We use this method to obtain four regioisomers of ADP-ribosylated ubiquitin (UbADPr), each modified with an ADP-ribosyl residue on a different arginine position within the ubiquitin (Ub) protein (Arg42, Arg54, Arg72, and Arg74) as the first reported examples of fully synthetic arginine-linked ADPr-modified proteins. We show the chemically prepared Arg-linked UbADPr to be accepted and processed by Legionella enzymes and compare the entire suite of four Arg-linked UbADPr regioisomers in a variety of biochemical experiments, allowing us to profile the activity and selectivity of Legionella pneumophila ligase and hydrolase enzymes.


Assuntos
Adenosina Difosfato Ribose , Arginina , Adenosina Difosfato Ribose/química , Arginina/metabolismo , ADP-Ribosilação , Ubiquitina/química , Proteínas Ubiquitinadas/metabolismo , Peptídeos/química
11.
Oncogene ; 41(46): 4994-5007, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36319669

RESUMO

Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma.


Assuntos
Metilação de DNA , Neuroblastoma , Humanos , Metilação de DNA/genética , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Neuroblastoma/metabolismo , Proliferação de Células/genética , Serina/metabolismo , Arginina/genética , Arginina/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
12.
Wiad Lek ; 75(9 pt 1): 2103-2107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36256936

RESUMO

OBJECTIVE: The aim: To analyze the features of changes in the functional state of the vascular endothelium of handball players in the dynamics of the training process, at different levels of the body's hypoxic state. PATIENTS AND METHODS: Materials and methods: Theoretical methods, the method of Corretti et al. with the use of high-resolution ultrasound, Fisher test with the calculation of the Fisher criterion and the Bland-Altman method. The study of the vasomotor function of the vascular endothelium was carried out of young men 18-20 y.o., who did not go in for sports and which were systematically played handball. The brachial artery diameter, maximum linear blood flow velocity, volumetric blood flow velocity were registered in the state of relative rest after artificially created reactive hyperemia. RESULTS: Results: The primary results obtained showed that in the process of long-term adaptation to systematic muscular work, a pronounced vasodilation effect was observed. Subsequent analyze of changes in the functional state of the vascular endothelium of young sportsmen during the macrocycle preparation different levels of the body's hypoxic state manifested the following. The young men-athletes had more pronounced vasodilation effect, the values of the linear and volumetric blood flow velocity both in the state of relative rest and at the peak of the artificially created hyperemia were significantly higher than in the young men, who did not go in for sports. CONCLUSION: Conclusions: Suggested that the systematic muscular work contributes to a significant intensification of the oxidation pathway of nitric oxide formation from L-arginine with the participation of endothelial NO-synthase.


Assuntos
Endotélio Vascular , Hiperemia , Masculino , Adolescente , Humanos , Óxido Nítrico/metabolismo , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/metabolismo , Vasodilatação , Hiperemia/metabolismo , Arginina/metabolismo
13.
Expert Rev Mol Med ; 24: e34, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36222080

RESUMO

Correct placental development and function are critical to both the mother's and the foetus' health during pregnancy. Placental function depends on the correct development of the vascular network, which requires proper angiogenesis. Impaired angiogenesis in the placenta can induce foetal growth restriction, preeclampsia, and even foetal death. Placental angiogenesis is finely controlled by ubiquitous and pregnancy-specific angiogenic factors. Jumonji domain-containing protein 6 (JMJD6) is a Fe (II)- and 2-oxoglutarate (2OG)-dependent oxygenase that catalyses arginine demethylation and lysine hydroxylation of histone and non-histone peptides. JMJD6 has been implicated in embryonic development, cellular proliferation and migration, self-tolerance induction in the thymus, and adipocyte differentiation. In this review we present JMJD6's structure and activity, as well as its role in angiogenesis, oxygen sensing, and adverse pregnancy outcomes related to placental development. Understanding the interaction between JMJD6 and other placental factors may identify potential therapeutic targets for correcting abnormal placental angiogenesis and function.


Assuntos
Histona Desmetilases com o Domínio Jumonji , Placentação , Arginina/metabolismo , Feminino , Humanos , Histona Desmetilases com o Domínio Jumonji/química , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Ácidos Cetoglutáricos/metabolismo , Lisina/metabolismo , Oxigênio/metabolismo , Placenta/metabolismo , Gravidez
14.
Food Res Int ; 161: 111848, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192900

RESUMO

The consumption of plant proteins is increasing worldwide. These proteins have an important role in human nutrition as well as in the technological properties of foods. Thus, there is a great interest in exploring new sources of plant proteins, such as macauba (Acrocomia aculeata), which is a promising tropical palm tree, native to Brazil, whose fruits are rich in oil, proteins and dietary fiber. Hence, the objective of this work was to obtain and evaluate the physico-chemical and techno-functional properties of the macauba kernel protein isolate (MKPI). Defatted macauba kernel flour was obtained and used to produce the MKPI by isoelectric precipitation. Then, the proximate composition, amino acid profile, and physico-chemical and techno-functional properties of the MKPI were determined. The MKPI stood out for its high protein content (94.9%) and high levels of arginine (16.21%) and glutamate (20.84%). The MKPI average isoelectric point was at pH 4.9 and its proteins showed low solubility in the pH range from 4.0 to 6.0. Moreover, the hydrophobicity of MKPI proteins was higher at pH 3.5 than at pH 7.0, and they had higher oil holding capacity (153.77%) than water holding capacity (97.29%). Regarding the MKPI emulsifying and gelling properties, emulsions with 0.5% and 1.0% of MKPI remained stable during storage and the minimum gelling concentration was 14%. Thus, the MKPI has a great potential to be produced and used by the food industry due to its nutritional and techno-functional properties.


Assuntos
Arecaceae , Aminoácidos/metabolismo , Arecaceae/química , Arginina/metabolismo , Fibras na Dieta/metabolismo , Glutamatos , Humanos , Proteínas de Plantas/metabolismo , Água/metabolismo
15.
Int J Mol Sci ; 23(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36233204

RESUMO

The contribution of nitric oxide synthases (NOSs) to the pathophysiology of several neuropsychiatric disorders is recognized, but the role of their regulators, dimethylarginine dimethylaminohydrolases (DDAHs), is less understood. This study's objective was to estimate DDAH1 and DDAH2 associations with biological processes implicated in major psychiatric disorders using publicly accessible expression databases. Since co-expressed genes are more likely to be involved in the same biologic processes, we investigated co-expression patterns with DDAH1 and DDAH2 in the dorsolateral prefrontal cortex in psychiatric patients and control subjects. There were no significant differences in DDAH1 and DDAH2 expression levels in schizophrenia or bipolar disorder patients compared to controls. Meanwhile, the data suggest that in patients, DDAH1 and DDHA2 undergo a functional shift mirrored in changes in co-expressed gene patterns. This disarrangement appears in the loss of expression level correlations between DDAH1 or DDAH2 and genes associated with psychiatric disorders and reduced functional similarity of DDAH1 or DDAH2 co-expressed genes in the patient groups. Our findings evidence the possible involvement of DDAH1 and DDAH2 in neuropsychiatric disorder development, but the underlying mechanisms need experimental validation.


Assuntos
Amidoidrolases , Produtos Biológicos , Transtornos Mentais , Amidoidrolases/genética , Amidoidrolases/metabolismo , Arginina/metabolismo , Humanos , Transtornos Mentais/genética , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase
16.
Int J Mol Sci ; 23(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36232396

RESUMO

The eukaryotic DNA replication fork is a hub of enzymes that continuously act to synthesize DNA, propagate DNA methylation and other epigenetic marks, perform quality control, repair nascent DNA, and package this DNA into chromatin. Many of the enzymes involved in these spatiotemporally correlated processes perform their functions by binding to proliferating cell nuclear antigen (PCNA). A long-standing question has been how the plethora of PCNA-binding enzymes exert their activities without interfering with each other. As a first step towards deciphering this complex regulation, we studied how Chromatin Assembly Factor 1 (CAF-1) binds to PCNA. We demonstrate that CAF-1 binds to PCNA in a heretofore uncharacterized manner that depends upon a cation-pi (π) interaction. An arginine residue, conserved among CAF-1 homologs but absent from other PCNA-binding proteins, inserts into the hydrophobic pocket normally occupied by proteins that contain canonical PCNA interaction peptides (PIPs). Mutation of this arginine disrupts the ability of CAF-1 to bind PCNA and to assemble chromatin. The PIP of the CAF-1 p150 subunit resides at the extreme C-terminus of an apparent long α-helix (119 amino acids) that has been reported to bind DNA. The length of that helix and the presence of a PIP at the C-terminus are evolutionarily conserved among numerous species, ranging from yeast to humans. This arrangement of a very long DNA-binding coiled-coil that terminates in PIPs may serve to coordinate DNA and PCNA binding by CAF-1.


Assuntos
Cromatina , Replicação do DNA , Aminoácidos/metabolismo , Arginina/metabolismo , Cromatina/genética , Cromatina/metabolismo , Fator 1 de Modelagem da Cromatina/química , Fator 1 de Modelagem da Cromatina/genética , Fator 1 de Modelagem da Cromatina/metabolismo , DNA/metabolismo , Humanos , Peptídeos/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
17.
Chem Commun (Camb) ; 58(86): 12054-12057, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36193595

RESUMO

Cyanobactins are linear and cyclic post-translationally modified peptides. Here we show that the prenyl-D-Arg-containing autumnalamide A is a member of the cyanobactin family. Biochemical assays demonstrate that the AutF prenyltransferase targets the guanidinium moiety in arginine and homoarginine and is a useful tool for biotechnological applications.


Assuntos
Vias Biossintéticas , Dimetilaliltranstransferase , Dimetilaliltranstransferase/química , Dimetilaliltranstransferase/metabolismo , Arginina/metabolismo , Homoarginina/metabolismo , Guanidina , Peptídeos Cíclicos/química
18.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36292941

RESUMO

Accessions of one plant species may show significantly different levels of susceptibility to stresses. The Arabidopsis thaliana accessions Col-0 and C24 differ significantly in their resistance to the pathogen Pseudomonas syringae pv. tomato (Pst). To help unravel the underlying mechanisms contributing to this naturally occurring variance in resistance to Pst, we analyzed changes in transcripts and compounds from primary and secondary metabolism of Col-0 and C24 at different time points after infection with Pst. Our results show that the differences in the resistance of Col-0 and C24 mainly involve mechanisms of salicylic-acid-dependent systemic acquired resistance, while responses of jasmonic-acid-dependent mechanisms are shared between the two accessions. In addition, arginine metabolism and differential activity of the biosynthesis pathways of aliphatic glucosinolates and indole glucosinolates may also contribute to the resistance. Thus, this study highlights the difference in the defense response strategies utilized by different genotypes.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Humanos , Arabidopsis/genética , Arabidopsis/metabolismo , Transcriptoma , Glucosinolatos/metabolismo , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/genética , Pseudomonas syringae/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Indóis/farmacologia , Indóis/metabolismo , Arginina/metabolismo , Resistência à Doença/genética , Ácido Salicílico/metabolismo
19.
Microbiol Spectr ; 10(5): e0204222, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36214676

RESUMO

Tuberculosis is a leading cause of worldwide infectious mortality. The prevalence of multidrug-resistant Mycobacterium tuberculosis infections drives an urgent need to exploit new drug targets. One such target is the ATP-dependent protease ClpC1P1P2, which is strictly essential for viability. However, few proteolytic substrates of mycobacterial ClpC1P1P2 have been identified to date. Recent studies in Bacillus subtilis have shown that the orthologous ClpCP protease recognizes proteolytic substrates bearing posttranslational arginine phosphorylation. While several lines of evidence suggest that ClpC1P1P2 is similarly capable of recognizing phosphoarginine-bearing proteins, the existence of phosphoarginine modifications in mycobacteria has remained in question. Here, we confirm the presence of posttranslational phosphoarginine modifications in Mycolicibacterium smegmatis, a nonpathogenic surrogate of M. tuberculosis. Using a phosphopeptide enrichment workflow coupled with shotgun phosphoproteomics, we identified arginine phosphosites on several functionally diverse targets within the M. smegmatis proteome. Interestingly, phosphoarginine modifications are not upregulated by heat stress, suggesting divergent roles in mycobacteria and Bacillus. Our findings provide new evidence supporting the existence of phosphoarginine-mediated proteolysis by ClpC1P1P2 in mycobacteria and other actinobacterial species. IMPORTANCE Mycobacteria that cause tuberculosis infections employ proteolytic pathways that modulate cellular behavior by destroying specific proteins in a highly regulated manner. Some proteolytic enzymes have emerged as novel antibacterial targets against drug-resistant tuberculosis infections. However, we have only a limited understanding of how these enzymes function in the cell and how they select proteins for destruction. Some proteolytic enzymes are capable of recognizing proteins that carry an unusual chemical modification, arginine phosphorylation. Here, we confirm the existence of arginine phosphorylation in mycobacterial proteins. Our work expands our understanding of a promising drug target in an important global pathogen.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Fosforilação , Proteoma/metabolismo , Fosfopeptídeos/metabolismo , Proteínas de Bactérias/metabolismo , Mycobacterium smegmatis/metabolismo , Arginina/metabolismo , Mycobacterium tuberculosis/metabolismo , Proteases Dependentes de ATP/metabolismo , Antibacterianos
20.
BMC Plant Biol ; 22(1): 496, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273172

RESUMO

Nearly 60 - 80 % of intron-containing plant genes undergo alternative splicing in response to either stress or plant developmental cues. RNA splicing is performed by a large ribonucleoprotein complex called the spliceosome in conjunction with associated subunits such as serine arginine (SR) proteins, all of which undergo extensive phosphorylation. In plants, there are three main protein kinase families suggested to phosphorylate core spliceosome subunits and related splicing factors based on orthology to human splicing-related kinases: the SERINE/ARGININE PROTEIN KINASES (SRPK), ARABIDOPSIS FUS3 COMPLEMENT (AFC), and Pre-mRNA PROCESSING FACTOR 4 (PRP4K) protein kinases. To better define the conservation and role(s) of these kinases in plants, we performed a genome-scale analysis of the three families across photosynthetic eukaryotes, followed by extensive transcriptomic and bioinformatic analysis of all Arabidopsis thaliana SRPK, AFC, and PRP4K protein kinases to elucidate their biological functions. Unexpectedly, this revealed the existence of SRPK and AFC phylogenetic groups with distinct promoter elements and patterns of transcriptional response to abiotic stress, while PRP4Ks possess no phylogenetic sub-divisions, suggestive of functional redundancy. We also reveal splicing-related kinase families are both diel and photoperiod regulated, implicating different orthologs as discrete time-of-day RNA splicing regulators. This foundational work establishes a number of new hypotheses regarding how reversible spliceosome phosphorylation contributes to both diel plant cell regulation and abiotic stress adaptation in plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Processamento Alternativo/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arginina/metabolismo , Proteínas Quinases/genética , Ribonucleoproteínas/genética , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA/genética , Fatores de Processamento de RNA/genética , Serina/genética , Estresse Fisiológico/genética
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