{"title":"Exploring claudin proteins: from sequence motifs to their impact on tight junction-mediated signaling pathways","authors":"Lingling Bao, Siqi Yang, Wenhua Zhao, Yongchun Zuo","doi":"10.1007/s00726-025-03479-w","DOIUrl":"10.1007/s00726-025-03479-w","url":null,"abstract":"<div><p>Claudin (CLDN) proteins are extensively studied due to their critical role in maintaining tissue barriers and cell polarity. However, significant gaps remain in understanding the functional mechanisms of their sequence motifs and the molecular mechanisms of their interactions with other tight junction proteins<b>.</b> This review systematically examines the multifunctional properties of the CLDN protein family from the perspectives of sequence and structure. During evolution, CLDN family members have developed highly conserved structural features, particularly key conserved sites within the first extracellular loop (ECL1) and the C-terminal PDZ-binding domain, which play a central role in regulating the barrier function of tight junctions, ion selectivity, and protein–protein interactions. Furthermore, the distribution pattern of acidic and basic amino acids in ECL1 has been shown to directly determine ion selectivity and paracellular permeability. Meanwhile, the assembly and functional stability of tight junctions are precisely regulated by the C-terminal PDZ-binding domain through its interactions with the ZO protein family. Additionally, the study further elucidates how CLDN proteins modulate critical signaling pathways governing cellular proliferation, survival, and permeability, thereby participating in diverse physiological and pathological processes. These insights have deepened the understanding of the functional diversity of CLDN proteins and provided a new theoretical basis for developing disease diagnostic markers and designing targeted treatment strategies based on CLDN proteins.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03479-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2025-09-18DOI: 10.1007/s00726-025-03475-0
Jiang Deng, Lihua Xu, Jun Zhou, He Huang
{"title":"Associations between XRCC1-Arg399Gln polymorphism and the risk of prostate cancer: an updated meta-analysis","authors":"Jiang Deng, Lihua Xu, Jun Zhou, He Huang","doi":"10.1007/s00726-025-03475-0","DOIUrl":"10.1007/s00726-025-03475-0","url":null,"abstract":"<div><p>The X-ray repair cross-complementary group 1 (XRCC1) gene 399 codon polymorphism may alter the structure of DNA repair enzymes to regulate DNA repair capacity. Impaired DNA repair ability can lead to the development of cancers such as prostate cancer (PCa). Although the association between the XRCC1 codon 399 polymorphism and the risk of PCa has been widely reported, the results have not been clear. Data were collected from PubMed, EMBASE, the Wanfang Database, CNKI and the Web of Science. A total of 20 case‒control studies were selected for inclusion in this updated analysis to determine the association between the XRCC1 codon 399 polymorphism and the risk of PCa. The crude odds ratio (OR) and 95% confidence interval (CI) were calculated using Stata (version 18) software to evaluate the association between the XRCC1-Arg399Gln polymorphism and prostate cancer. We identified 20 eligible reports that included 5803 cases of prostate cancer and 5470 controls. Our meta-analysis revealed a significant association between the XRCC1-Arg399Gln polymorphism and the risk of prostate cancer. In particular, according to the recessive models, this polymorphism was associated with a significantly increased prevalence of prostate cancer in Asian populations (AA versus AG + GG: OR = 1.255, 95% CI = 1.063–1.481, <i>P</i> = 0.507, I<sup>2</sup>, < 25%). Based on these results, the XRCC1-Arg399Gln polymorphism may be a risk factor for prostate cancer and can be used as a biomarker to predict the prognosis of prostate cancer.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03475-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2025-09-18DOI: 10.1007/s00726-025-03481-2
Marek Pająk, Elżbieta Kamysz, Marcin Banach, Wojciech Michał Jankowski, Aleksandra Tarasiuk-Zawadzka, Jakub Fichna, Magdalena Woźniczka
{"title":"Protolytic properties and biological activity of spinorphin and its butyric acid derivatives in aqueous solution","authors":"Marek Pająk, Elżbieta Kamysz, Marcin Banach, Wojciech Michał Jankowski, Aleksandra Tarasiuk-Zawadzka, Jakub Fichna, Magdalena Woźniczka","doi":"10.1007/s00726-025-03481-2","DOIUrl":"10.1007/s00726-025-03481-2","url":null,"abstract":"<div><p>The present work describes the protolytic properties and in vitro biological activity of spinorphin (Leu-Val-Val-Tyr-Pro-Trp-Thr) and three spinorphin derivatives containing butyric acid residue: Butyryl-Lys-Lys-Leu-Leu-Val-Tyr-Pro-Trp-Thr, Butyryl-Lys-Lys-Leu-Val-Val-Tyr-Pro-Trp-Thr (butyric acid bound to the α-amino group of lysine), Lys(Butyryl)-Lys-Leu-Val-Val-Tyr-Pro-Trp-Thr (butyric acid bound to the ε-amino group of lysine) in an aqueous solution. The overall protonation constants and the stepwise dissociation constants of the ligands studied were calculated by the potentiometric method. The percentage of each species formed was estimated from the species distribution curves as a function of pH. The biological activity of all tested compounds was characterized in vitro, in the neutral red uptake and Griess assay tests in RAW264.7 macrophage cell line. The three protonation constants for spinorphin and four for its derivatives suggest that metal ions may bind to these peptides and form complexes by coordination with the functional groups of the respective amino acid residues. In vitro biological activity tests suggest that two peptides deserve attention for their potential anti-inflammatory role.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03481-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rational designing and synthesizing an antimicrobial peptide from bovine milk casein and evaluating its biological properties","authors":"Seyed Reza Pourhosseini, Bahman Akbari, Elahe Ghods, Kamal Veisi, Hamid Madanchi","doi":"10.1007/s00726-025-03477-y","DOIUrl":"10.1007/s00726-025-03477-y","url":null,"abstract":"<div><p>The overuse of antibiotics has led to a growing crisis—antimicrobial resistance, making it harder to treat infections and pushing scientists to find new solutions. Among the most promising alternatives are bioactive peptides, especially antimicrobial peptides, which offer broad-spectrum activity with a lower risk of resistance. One exciting source of these peptides is milk, particularly casein-derived peptides, which naturally possess antimicrobial properties. This study focused on bovine milk casein to design and synthesize a novel antimicrobial peptide. We evaluated several properties, such as antimicrobial activity, cytotoxicity, stability, and structure, using computational predictions to select the most promising candidate. The peptide NCP1 emerged as the best option and was synthesized for lab testing. Our results showed that NCP1 has antifungal activity and effectively stops the growth of <i>Candida albicans</i> with a minimum fungicidal concentration (MFC) of 250 µg/mL in less than four hours. It also prevented biofilm formation, interacted with DNA, and bound to ergosterol, ultimately damaging the fungal cell wall. Additionally, NCP1 demonstrated feeble antibacterial effects, particularly against <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. However, its antibacterial impact weakened over time due to interactions with environmental salts. Since the NCP1 peptide has low cytotoxicity and kills the yeasts selectively, further refinements to improve its potency and stability could pave the way for our future study of the presentation of a potent antimicrobial peptide.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03477-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2025-09-13DOI: 10.1007/s00726-025-03476-z
Arturs Zemitis, Lelde Svjascenkova, Sandra Bleidele, Alberts Veitners, Juris Vanags, Kristaps Klavins, Guna Laganovska
{"title":"Metabolic alterations in diabetic patients: aqueous humor profiling for biomarker discovery","authors":"Arturs Zemitis, Lelde Svjascenkova, Sandra Bleidele, Alberts Veitners, Juris Vanags, Kristaps Klavins, Guna Laganovska","doi":"10.1007/s00726-025-03476-z","DOIUrl":"10.1007/s00726-025-03476-z","url":null,"abstract":"<div><p>Diabetic retinopathy, a leading cause of vision loss in working-age populations, is a severe complication of diabetes mellitus. Metabolomics, a key approach in systems biology, offers insights into the complex pathophysiology of diabetes by analyzing low-molecular-weight compounds in biological contexts. This study investigated metabolite alterations in the aqueous humor of diabetic and non-diabetic patients undergoing cataract surgery to identify potential biomarkers associated with diabetes. Aqueous humor samples from 191 patients (48 diabetic, 143 non-diabetic) were analyzed using targeted liquid chromatography-mass spectrometry. Metabolite data were normalized and statistically evaluated using univariate analysis, including fold change calculations, t-tests, and volcano plots. Pathway enrichment analysis was performed using KEGG, SMPDB, and RaMP-DP databases. Key findings revealed differential abundance of several metabolites, including upregulated 3-hydroxykynurenine, histamine, and octanoylcarnitine, and downregulated putrescine in diabetic patients. Although some metabolites exhibited low p-values (< 0.05), high FDR limited the statistical robustness of these findings. Quantitative enrichment analysis suggested potential involvement of the kynurenine pathway and tryptophan catabolism in diabetes-related metabolic changes. The study highlights the potential roles of these metabolites in diabetes-related ocular changes, supported by prior research linking them to oxidative stress, inflammation, and metabolic dysregulation. Antioxidative therapies targeting diabetes-associated metabolic alterations may offer potential for mitigating diabetes-related complications. High FDR underscores the need for cautious interpretation and further validation in larger cohorts. Future studies should focus on longitudinal analyses and mechanistic investigations to clarify the diagnostic and prognostic potential of these metabolites in diabetic retinopathy and other diabetes-related complications.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03476-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the therapeutic potential of L-arginine in chronic anal fissure management: a comprehensive review","authors":"Nogol Motamed-Gorji, Mohsen Masoodi, Masoumeh Khalighi Sikaroudi, Shahram Agah, Nikta Masoodi","doi":"10.1007/s00726-025-03478-x","DOIUrl":"10.1007/s00726-025-03478-x","url":null,"abstract":"<div><p>Anal fissure causes pain and bleeding during or after bowel movements, significantly impacting individuals’ quality of life. Current treatments aim to interrupt this cycle but have associated risks and limitations. The emergence of arginine, crucial for protein creation and nitric oxide (NO) production, presents an intriguing therapeutic avenue by the impact on reducing anal sphincter pressure and enhancing anoderm blood flow, due to its roles in vasodilation, anti-inflammatory responses, and collagen synthesis, which can promote wound healing and highlighting its potential as an alternative therapy. However, the effectiveness of oral supplementation remains debated, indicating the need for further elucidation of its mechanisms. Its multifaceted mechanisms can present an exciting avenue for nuanced treatments, urging further exploration to refine its role in chronic anal fissure management. This review comprehensively explores the therapeutic landscape of L-arginine in chronic anal fissure management, integrating recent research studies and clinical investigations.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03478-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2025-08-22DOI: 10.1007/s00726-025-03474-1
Shaohua Xu, Kai Liu, Zhao Chen, Weijian Tang, Zhoumiao Chen
{"title":"IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma","authors":"Shaohua Xu, Kai Liu, Zhao Chen, Weijian Tang, Zhoumiao Chen","doi":"10.1007/s00726-025-03474-1","DOIUrl":"10.1007/s00726-025-03474-1","url":null,"abstract":"<div><p>ABCA1 is a key protein in maintaining cholesterol homeostasis, and its abnormal expression is associated with the progression of many cancers. Nonetheless, the specific molecular mechanisms by which ABCA1 facilitates the development of LUAD remain largely unexplored, necessitating further in-depth investigation. The TCGA-LUAD database was used to analyze the expression of ABCA1 in LUAD tissues. Subsequently, a cell model with overexpressed ABCA1 was constructed for verification through cell experiments. Cell function was evaluated using the Transwell assay and the colony formation assay. Intracellular cholesterol levels were detected using a kit. At the same time, the online database RM2 Target was employed to predict upstream factors that may have a methylation regulatory relationship with ABCA1. On this basis, Dot blot and MeRIP-qPCR techniques were employed to determine the degree of m6A modification. To clarify the mechanism of IGF2BP1 regulating ABCA1 through the m6A pathway, RNA pull-down binding experiments were carried out, and changes in mRNA stability were assessed using actinomycin D treatment. Finally, the biological function of the IGF2BP1/ABCA1 signaling axis during the growth and metastasis of LUAD in vivo was evaluated by establishing a xenograft animal model. Bioinformatics analysis and cell experimental results confirmed the low expression of ABCA1 in LUAD tissues and cells. ABCA1 significantly inhibited cell proliferation, migration, and invasion capabilities, promoted apoptosis, and reduced intracellular cholesterol levels. From a molecular perspective, IGF2BP1 recognized and bound to methylation sites on ABCA1 mRNA, thereby accelerating its degradation process, resulting in a substantial decrease in the stability of ABCA1 mRNA. Moreover, in vivo and in vitro experiments further confirmed that IGF2BP1 affected cholesterol metabolism by regulating the expression of ABCA1, thereby facilitating the malignant progression of LUAD. Overall, our research revealed that IGF2BP1 affects cholesterol metabolism by reducing the stability of ABCA1 mRNA through m6A modification, thereby boosting the malignant progression of LUAD and formulating a theoretical basis for subsequent LUAD treatment.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03474-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2025-08-18DOI: 10.1007/s00726-025-03473-2
Karolina Banaś, Paweł Lenartowicz, Dawid Siodłak
{"title":"Insight into the structure of antitubercular Callyaerins: conformational studies and synthesis of a unique dehydroamino acid, β-aminodehydroalanine","authors":"Karolina Banaś, Paweł Lenartowicz, Dawid Siodłak","doi":"10.1007/s00726-025-03473-2","DOIUrl":"10.1007/s00726-025-03473-2","url":null,"abstract":"<div><p>β-Aminodehydroalanine, ΔAla(β-NH), (2,3-diaminoprop-2-enoic acid), is a unique dehydroamino acid and a central component of Callyaerins A-M and Callynormine A. The presence of this unusual structural element containing an enamine functional group may be related to the antitubercular activity of Callyaerins. According to The WHO Global Tuberculosis Report tuberculosis is the second leading cause of death worldwide caused by a single infectious agent. Therefore, it is essential to understand the molecular structure of these peptides in more detail. To investigate the conformational properties of the ΔAla(β-NH) residue, a series of model compounds: Ac-(Z/E)-ΔAla(β-NHMe)-NHMe, Ac-(Z/E)-ΔAla(β-NHMe)-NMe<sub>2</sub>, Boc-Gly-(Z)-ΔAla(β-NHMe)-OMe, and Boc-Gly-(Z)-ΔAla(β-Leu-OMe)-OMe, were selected for quantum chemical calculations and/or synthesized. Two conformations, β2 (φ,ψ ~ − 120°, 20°) and α (φ,ψ ~ − 70°, − 15°) are predicted as the most preferable, regardless of the geometry of isomer (Z/E), polarity of environment, and order (2°/3°) of C-terminal amide group. The N–H⋯O hydrogen bond involving the N–H group in the β position of the side chain as a donor is a significant stabilizing factor. The Z isomer is predicted to be the most stable and has been synthesized. The following synthesis method is proposed: Ser → ΔAla → ΔAla(β-Br) → ΔAla(β-NH). The advantages of the proposed method are: (i) serine as the starting substrate, (ii) mild alkaline conditions, (iii) avoidance of the reactive intermediate α-formylglycine.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03473-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2025-08-09DOI: 10.1007/s00726-025-03472-3
Yi-Chen Li, Hong-Kai Yuan, Lei-Miao Yin
{"title":"Post-translational modifications of ezrin: a crucial regulator for diseases","authors":"Yi-Chen Li, Hong-Kai Yuan, Lei-Miao Yin","doi":"10.1007/s00726-025-03472-3","DOIUrl":"10.1007/s00726-025-03472-3","url":null,"abstract":"<div><p>Ezrin is a crucial structural protein that connects the plasma membrane to the actin cytoskeleton to maintain cell shape, adhesion, and motility. Post-translational modifications (PTMs) play a key role in the regulation of various biological functions and have been implicated in a range of pathological conditions. With the help of PTMs, ezrin not only plays a structural role in connecting the cell membrane to F-actin, but also participates in transmitting cellular signals including those related to inflammatory responses. In this study, we reviewed the key sites and domains involved in the different PTMs of ezrin, including acetylation, lactylation and phosphorylation. We analyzed the regulation of biological processes mediated by different PTMs of ezrin, such as cell migration, inflammation regulation and cell stiffness. In addition, we examined the mutual regulatory effects of different modifications of ezrin, including regulation of ezrin phosphorylation by kinases and phosphatases, and so on. Increasing evidence suggests that PTMs of ezrin are involved in cancer, respiratory diseases and urological diseases. These studies provide novel insights into the design of new disease treatment strategies targeting ezrin.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2025-08-05DOI: 10.1007/s00726-025-03467-0
Saranya Prashath
{"title":"The effect of L-Arg supplementation on L-Arg/NO metabolic and AMPK/ACC-1 signalling pathways in adipose cells (3T3 L1)","authors":"Saranya Prashath","doi":"10.1007/s00726-025-03467-0","DOIUrl":"10.1007/s00726-025-03467-0","url":null,"abstract":"<div><p>L-arginine (L-Arg) is metabolised in the cell to generate nitric oxide (NO) and citrulline via nitric oxide synthase (NOS). NO is an important cellular signalling molecule that regulates lipid and glucose metabolism. The biological availability of NO is affected by the NOS inhibitor; N<sup>G</sup>-nitro-L-Arg methyl ester (L-NAME) and the external NO donor; S-nitroso-N-acetyl-D, L-penicillamine (SNAP). Mouse adipocyte 3T3 L1 cells were cultured with 0, 400 and 800 µM L-Arg or control complete DMEM media. The impact of L-NAME (4 mM), and SNAP (100 µM) was also analysed. The cell fitness was similar and the mRNA levels of AMPK was increased and ACC-1 was decreased, whilst the activation of AMPK and ACC-1 was decreased upon the addition of exogenous L-Arg. Transcript and protein levels of AMPK and ACC-1 were regulated by addition of L-NAME and SNAP, however the impact of these targets was related to the concentration of L-Arg added to the cells and the culture time point of analysis. NO in the form of NO<sub>2</sub><sup>−</sup> in cell culture supernatant was elevated in 400 and 800 µM L-Arg cultures. L-NAME significantly inhibited NO production from adipose cells in a time-dependent manner and subsequently impacted AMPK and ACC expression. Associated with these changes were changed in the concentration of L-Arg, L-Cit and L-Orn in the culture media. Collectively, these results show that excess L-Arg is sensed by the cell which then regulates AMPK and ACC-1 expression in response. The findings could have implications in modulation of signalling pathways for treating obesity and obesity induced diabetic mellitus.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}