Amino AcidsPub Date : 2024-08-29DOI: 10.1007/s00726-024-03415-4
Michaela Masopustová, Adam Goga, Miroslav Soural, Martina Kopečná, Marek Šebela
{"title":"N-carboxyacyl and N-α-aminoacyl derivatives of aminoaldehydes as shared substrates of plant aldehyde dehydrogenases 10 and 7","authors":"Michaela Masopustová, Adam Goga, Miroslav Soural, Martina Kopečná, Marek Šebela","doi":"10.1007/s00726-024-03415-4","DOIUrl":"10.1007/s00726-024-03415-4","url":null,"abstract":"<div><p>Aldehyde dehydrogenases (ALDHs) represent a superfamily of enzymes, which oxidize aldehydes to the corresponding acids. Certain families, namely ALDH9 and ALDH10, are best active with ω-aminoaldehydes arising from the metabolism of polyamines such as 3-aminopropionaldehyde and 4-aminobutyraldehyde. Plant ALDH10s show broad specificity and accept many different aldehydes (aliphatic, aromatic and heterocyclic) as substrates. This work involved the above-mentioned aminoaldehydes acylated with dicarboxylic acids, phenylalanine, and tyrosine. The resulting products were then examined with native ALDH10 from pea and recombinant ALDH7s from pea and maize. This investigation aimed to find a common efficient substrate for the two plant ALDH families. One of the best natural substrates of ALDH7s is aminoadipic semialdehyde carrying a carboxylic group opposite the aldehyde group. The substrate properties of the new compounds were demonstrated by mass spectrometry of the reaction mixtures, spectrophotometric assays and molecular docking. The <i>N</i>-carboxyacyl derivatives were good substrates of pea ALDH10 but were only weakly oxidized by the two plant ALDH7s. The <i>N</i>-phenylalanyl and <i>N</i>-tyrosyl derivatives of 3-aminopropionaldehyde were good substrates of pea and maize ALDH7. Particularly the former compound was converted very efficiently (based on the <i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub> ratio), but it was only weakly oxidized by pea ALDH10. Although no compound exhibited the same level of substrate properties for both ALDH families, we show that these enzymes may possess more common substrates than expected.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103595","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 : 2024-08-28DOI: 10.1007/s00726-024-03417-2
Philipp Reifenberg, Aline Zimmer
{"title":"Branched-chain amino acids: physico-chemical properties, industrial synthesis and role in signaling, metabolism and energy production","authors":"Philipp Reifenberg, Aline Zimmer","doi":"10.1007/s00726-024-03417-2","DOIUrl":"10.1007/s00726-024-03417-2","url":null,"abstract":"<div><p>Branched-chain amino acids (BCAAs)—leucine (Leu), isoleucine (Ile), and valine (Val)—are essential nutrients with significant roles in protein synthesis, metabolic regulation, and energy production. This review paper offers a detailed examination of the physico-chemical properties of BCAAs, their industrial synthesis, and their critical functions in various biological processes. The unique isomerism of BCAAs is presented, focusing on analytical challenges in their separation and quantification as well as their solubility characteristics, which are crucial for formulation and purification applications. The industrial synthesis of BCAAs, particularly using bacterial strains like <i>Corynebacterium glutamicum</i>, is explored, alongside methods such as genetic engineering aimed at enhancing production, detailing the enzymatic processes and specific precursors. The dietary uptake, distribution, and catabolism of BCAAs are reviewed as fundamental components of their physiological functions. Ultimately, their multifaceted impact on signaling pathways, immune function, and disease progression is discussed, providing insights into their profound influence on muscle protein synthesis and metabolic health. This comprehensive analysis serves as a resource for understanding both the basic and complex roles of BCAAs in biological systems and their industrial application.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091425","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 : 2024-08-25DOI: 10.1007/s00726-024-03410-9
Théoneste Umumararungu, Noël Gahamanyi, Janvier Mukiza, Gratien Habarurema, Jonathan Katandula, Alexis Rugamba, Vedaste Kagisha
{"title":"Proline, a unique amino acid whose polymer, polyproline II helix, and its analogues are involved in many biological processes: a review","authors":"Théoneste Umumararungu, Noël Gahamanyi, Janvier Mukiza, Gratien Habarurema, Jonathan Katandula, Alexis Rugamba, Vedaste Kagisha","doi":"10.1007/s00726-024-03410-9","DOIUrl":"10.1007/s00726-024-03410-9","url":null,"abstract":"<div><p>Proline is a unique amino acid in that its side-chain is cyclised to the backbone, thus giving proline an exceptional rigidity and a considerably restricted conformational space. Polyproline forms two well-characterized helical structures: a left-handed polyproline helix (PPII) and a right-handed polyproline helix (PPI). Usually, sequences made only of prolyl residues are in PPII conformation, but even sequences not rich in proline but which are rich in glycine, lysine, glutamate, or aspartate have also a tendency to form PPII helices. Currently, the only way to study unambiguously PPII structure in solution is to use spectroscopies based on optical activity such as circular dichroism, vibrational circular dichroism and Raman optical activity. The importance of the PPII structure is emphasized by its ubiquitous presence in different organisms from yeast to human beings where proline-rich motifs and their binding domains are believed to be involved in vital biological processes. Some of the domains that are bound by proline-rich motifs include SH3 domains, WW domains, GYF domains and UEV domains, etc. The PPII structure has been demonstrated to be essential to biological activities such as signal transduction, transcription, cell motility, and immune response.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054710","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 : 2024-08-24DOI: 10.1007/s00726-024-03411-8
Dagmara Tymecka, Patrycja Redkiewicz, Piotr F. J. Lipiński, Aleksandra Misicka
{"title":"Peptidomimetic inhibitors of the VEGF-A165/NRP-1 complex obtained by modification of the C-terminal arginine","authors":"Dagmara Tymecka, Patrycja Redkiewicz, Piotr F. J. Lipiński, Aleksandra Misicka","doi":"10.1007/s00726-024-03411-8","DOIUrl":"10.1007/s00726-024-03411-8","url":null,"abstract":"<div><p>Inhibitors of the interaction between Neuropilin-1 (NRP-1) and Vascular Endothelial Growth Factor-A<sub>165</sub> (VEGF-A<sub>165</sub>) hold significant promise as therapeutic and diagnostic agents directed against cancers overexpressing NRP-1. In our efforts in this field, a few series of strong and fairly stable peptide-like inhibitors of the general formula Lys(Har)<sup>1</sup>-Xaa<sup>2</sup>-Xaa<sup>3</sup>-Arg<sup>4</sup> have been previously discovered. In the current work, we focused on Lys(Har)-Dap/Dab-Pro-Arg sequence. The aim was to examine whether replacing C-terminal Arg with its homologs and mimetics would yield more stable yet still potent inhibitors. Upon considering the results of modelling and other factors, ten novel analogues with Xaa<sup>4</sup> = homoarginine (Har), 2-amino-4-guanidino-butyric acid (Agb), 2-amino-3-guanidino-propionic acid (Agp), citrulline (Cit), 4-aminomethyl-phenylalanine [Phe(4-CH<sub>2</sub>-NH<sub>2</sub>)] were designed, synthesized and evaluated. Two of the proposed modifications resulted in inhibitors with activity slightly lower [e.g. IC<sub>50</sub> = 14.3 μM for Lys(Har)-Dab-Pro-Har and IC<sub>50</sub> = 19.8 μM for Lys(Har)-Dab-Pro-Phe(4-CH<sub>2</sub>-NH<sub>2</sub>)] than the parent compounds [e.g. IC<sub>50</sub> = 4.7 μM for Lys(Har)-Dab-Pro-Arg]. What was a surprise to us, the proteolytic stability depended more on position two of the sequence than on position four. The Dab<sup>2</sup>-analogues exhibited half-life times beyond 60 h. Our results build up the knowledge on the structural requirements that effective VEGF-A<sub>165</sub>/NRP-1 inhibitors should fulfil.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054709","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 : 2024-07-27DOI: 10.1007/s00726-024-03408-3
Tiantian Liu, Yaya Xu, Shaohua Hu, Shuyun Feng, Hong Zhang, Xiaodong Zhu, Chunxia Wang
{"title":"Alanine, a potential amino acid biomarker of pediatric sepsis: a pilot study in PICU","authors":"Tiantian Liu, Yaya Xu, Shaohua Hu, Shuyun Feng, Hong Zhang, Xiaodong Zhu, Chunxia Wang","doi":"10.1007/s00726-024-03408-3","DOIUrl":"10.1007/s00726-024-03408-3","url":null,"abstract":"<div><p>Sepsis is characterized by a metabolic disorder of amino acid occurs in the early stage; however, the profile of serum amino acids and their alterations associated with the onset of sepsis remain unclear. Thus, our objective is to identify the specific kinds of amino acids as diagnostic biomarkers in pediatric patients with sepsis. Serum samples were collected from patients with sepsis admitted to the pediatric intensive care unit (PICU) between January 2019 and December 2019 on the 1<sup>st</sup>, 3<sup>rd</sup> and 7<sup>th</sup> day following admission. Demographic and laboratory variables were also retrieved from the medical records specified times. Serum amino acid concentrations were detected by UPLC-MS/MS system. PLS-DA (VIP > 1.0) and <i>Kruskal-Wallis</i> test (<i>p</i> < 0.05) were employed to identify potential biomarkers. <i>Spearman’s</i> rank correlation analysis was conducted to find the potential association between amino acid levels and clinical features. The diagnostic utility for pediatric sepsis was assessed using receiver operating characteristic (<i>ROC</i>) curve analysis. Most of amino acid contents in serum were significantly decreased in patients with sepsis, but approached normal levels by the seventh day post-diagnosis. Threonine (THR), lysine (LYS), valine (VAL) and alanine (ALA) emerged as potential biomarkers related for sepsis occurrence, though they were not associated with PELOD/PELOD-2 scores. Moreover, alterations in serum THR, LYS and ALA were linked to complications of brain injury, and serum ALA levels were also related to sepsis-associated acute kidney injury. Further analysis revealed that ALA was significantly correlated with the <i>Glasgow</i> score, serum lactate and glucose levels, C-reactive protein (CRP), and other indicators for liver or kidney dysfunction. Notably, the area under the <i>ROC</i> curve (AUC) for ALA in distinguishing sepsis from healthy controls was 0.977 (95% <i>CI</i>: 0.925-1.000). The serum amino acid profile of children with sepsis is significantly altered compared to that of healthy controls. Notably, ALA shows promise as a potential biomarker for the early diagnosis in septic children.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764891","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 : 2024-07-26DOI: 10.1007/s00726-024-03402-9
Xiaoyan Chen, Jiahui Jin, Rui Chang, Xing Yang, Na Li, Xi Zhu, Linlin Ma, Yanfei Li
{"title":"Targeting the sulfur-containing amino acid pathway in leukemia","authors":"Xiaoyan Chen, Jiahui Jin, Rui Chang, Xing Yang, Na Li, Xi Zhu, Linlin Ma, Yanfei Li","doi":"10.1007/s00726-024-03402-9","DOIUrl":"10.1007/s00726-024-03402-9","url":null,"abstract":"<div><p>sulfur-containing amino acids have been reported to patriciate in gene regulation, DNA methylation, protein synthesis and other physiological or pathological processes. In recent years, metabolism-related molecules of sulfur-containing amino acids affecting the occurrence, development and treatment of tumors have been implicated in various disorders, especially in leukemia. Here, we summarize current knowledge on the sulfur-containing amino acid metabolism pathway in leukemia and examine ongoing efforts to target this pathway, including treatment strategies targeting (a) sulfur-containing amino acids, (b) metabolites of sulfur-containing amino acids, and (c) enzymes and cofactors related to sulfur-containing amino acid metabolism in leukemia. Future leukemia therapy will likely involve innovative strategies targeting the sulfur-containing amino acid metabolism pathway.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764892","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":"Differentiated metabolomic profiling reveals plasma amino acid signatures for primary glomerular disease","authors":"Jiao Wang, Chunyu Zhou, Liqian Lu, Shoujun Wang, Qing Zhang, Zhangsuo Liu","doi":"10.1007/s00726-024-03407-4","DOIUrl":"10.1007/s00726-024-03407-4","url":null,"abstract":"<div><p>Primary glomerular disease (PGD) is an idiopathic cause of renal glomerular lesions that is characterized by proteinuria or hematuria and is the leading cause of chronic kidney disease (CKD). The identification of circulating biomarkers for the diagnosis of PGD requires a thorough understanding of the metabolic defects involved. In this study, ultra-high performance liquid chromatography–tandem mass spectrometry was performed to characterize the amino acid (AA) profiles of patients with pathologically diagnosed PGD, including minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), membranous nephropathy, and immunoglobulin A nephropathy. The plasma concentrations of asparagine and ornithine were low, and that of aspartic acid was high, in patients with all the pathologic types of PGD, compared to healthy controls. Two distinct diagnostic models were generated using the differential plasma AA profiles using logistic regression and receiver operating characteristic analyses, with areas under the curves of 1.000 and accuracies up to 100.0% in patients with MCD and FSGS. In conclusion, the progression of PGD is associated with alterations in AA profiles, The present findings provide a theoretical basis for the use of AAs as a non-invasive, real-time, rapid, and simple biomarker for the diagnosis of various pathologic types of PGD.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632418","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 : 2024-07-15DOI: 10.1007/s00726-024-03404-7
Qi Ma, Fei Ma, Bin Zhang, Yonglei Zhang, Liangqun Peng, Xiangnan Li
{"title":"The short peptide encoded by long non-coding RNA RNF217-AS1 inhibits stomach cancer tumorigenesis, macrophage recruitment, and pro-inflammatory responses","authors":"Qi Ma, Fei Ma, Bin Zhang, Yonglei Zhang, Liangqun Peng, Xiangnan Li","doi":"10.1007/s00726-024-03404-7","DOIUrl":"10.1007/s00726-024-03404-7","url":null,"abstract":"<div><p>Certain long non-coding RNAs (lncRNAs) have potential peptide-coding abilities. Here, the role and molecular basis of the RNF217-AS1-encoded peptide in stomach cancer (SC) tumorigenesis were explored. Here, lncRNAs associated with SC pathogenesis and macrophage infiltration and lncRNAs with peptide-coding potential were searched by bioinformatics analysis. The gene mRNA and protein levels were examined by RT-qPCR and western blot assays, respectively. Cell viability, migratory, and invasive abilities were measured by CCK-8, Transwell migration, and Transwell invasion assays, respectively. The potential biological processes related to lncRNA RNF217-AS1 were identified by single-gene GSEA analysis. The effect of RNF217-AS1-encoded peptide on SC tumorigenesis was examined by mouse xenograft experiments. The results showed that lncRNA NR2F1-AS1 and RNF217-AS1 were differentially expressed and associated with macrophage infiltration in SC, and they had the ability to translate into short peptides. The RNF217-AS1 ORF-encoded peptide could reduce SC cell viability, inhibit cell migration and invasion, as well as hinder the development of SC xenograft tumors. The RNF217-AS1 ORF-encoded peptide in human SC AGS cells suppressed THP-1 cell migration, triggered the differential expression of CXCL1/CXCL2/CXCL8/CXCL12, and inactivated the TLR4/NF-κB/STAT1 signaling pathways. As a conclusion, the RNF217-AS1 ORF-encoded peptide hindered SC progression in vitro and in vivo and suppressed macrophage recruitment and pro-inflammatory responses in SC.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615788","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":"PEGylation renders carnosine resistant to hydrolysis by serum carnosinase and increases renal carnosine levels","authors":"Shiqi Zhang, Guang Yang, Qinqin Zhang, Yuying Fan, Mingna Tang, Liuhai Shen, Dongchun Zhu, Guiyang Zhang, Benito Yard","doi":"10.1007/s00726-024-03405-6","DOIUrl":"10.1007/s00726-024-03405-6","url":null,"abstract":"<div><p>Carnosine’s protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH<sub>2</sub>). PEGylated carnosine (PEG-car) was used to study the hydrolysis of carnosine by human serum as well as to compare the pharmacokinetics of PEG-car and L-carnosine in mice after intravenous (IV) injection. While L-carnosine was rapidly hydrolyzed in human serum, PEG-car was highly resistant to hydrolysis. Addition of unconjugated PEG to carnosine or PEG-car did not influence hydrolysis of carnosine in serum. In mice PEG-car and L-carnosine exhibited similar pharmacokinetics in serum but differed in half-life time (t<sub>1/2</sub>) in kidney, with PEG-car showing a significantly higher t<sub>1/2</sub> compared to L-carnosine. Hence, PEGylation of carnosine is an effective approach to prevent carnosine degradations and to achieve higher renal carnosine levels. However, further studies are warranted to test if the protective properties of carnosine are preserved after PEGylation.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496891","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":"In vitro and in vivo studies on exogenous polyamines and α-difluoromethylornithine to enhance bone formation and suppress osteoclast differentiation","authors":"Chien-Ching Lee, Chia-Chun Chuang, Chung-Hwan Chen, Yuan-Pin Huang, Chiao-Yi Chang, Pei-Yi Tung, Mon-Juan Lee","doi":"10.1007/s00726-024-03403-8","DOIUrl":"10.1007/s00726-024-03403-8","url":null,"abstract":"<div><p>Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454691","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}