Archives of biochemistry and biophysics最新文献

{"title":"Binding of glyceraldehyde-3-phosphate dehydrogenase to G-actin promotes the transnitrosylation reaction","authors":"Maria V. Medvedeva ,&nbsp;Marina V. Serebryakova ,&nbsp;Alexander M. Matyushenko ,&nbsp;Victoria V. Nefedova ,&nbsp;Vladimir I. Muronetz ,&nbsp;Elena V. Schmalhausen","doi":"10.1016/j.abb.2024.110189","DOIUrl":"10.1016/j.abb.2024.110189","url":null,"abstract":"<div><div>In this study, we investigated formation of the complex between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and actin and the possibility of nitrosyl group transfer between GAPDH and actin. A complex of GAPDH with beta-actin was isolated from lysates of HEK293T cells using immunoprecipitation with antibodies against GAPDH or against beta-actin. The treatment of the cells with H₂O₂ or NO donor did not affect the formation of the complex. Investigation of the interaction between purified GAPDH and muscle alpha-actin showed that GAPDH interacts better with globular (G-) actin than with fibrillary actin, and oxidation/reduction of GAPDH does not affect this interaction. S-nitrosylated GAPDH (GAPDH-SNO) was partially reactivated in the presence of G-actin, which was accompanied by denitrosylation of GAPDH and sulfenation of G-actin. The sulfenated cysteine residue in G-actin was identified by MALDI-TOF MS analysis as C-terminal Cys374. Based on the properties of nitrosothiols, we assume that the cysteine-sulfenic acid in actin is a product of spontaneous hydrolysis of S-nitrosylated cysteine residue. The obtained results suggest that Cys374 in actin is S-nitrosylated during the incubation with GAPDH-SNO (transnitrosylation reaction). The transfer of the NO-group from GAPDH-SNO to the C-terminal Cys374 of actin suggests that upon interaction with GAPDH, the C-terminus of actin is located in the active center of GAPDH in the proximity to the catalytic Cys152. It is possible that the ability of GAPDH-SNO to nitrosylate actin contributes to the redox regulation of actin-controlled signaling pathways.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"762 ","pages":"Article 110189"},"PeriodicalIF":3.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of the novel amylin and calcitonin receptor activators by peptide mutagenesis","authors":"Sangmin Lee","doi":"10.1016/j.abb.2024.110191","DOIUrl":"10.1016/j.abb.2024.110191","url":null,"abstract":"<div><div>The amylin peptide hormone receptor is the complex of the calcitonin peptide hormone receptor and an accessory protein. The calcitonin receptor activation controls calcium homeostasis, while it also functions as the main component of the amylin receptor. Amylin receptor activation in brains controls blood glucose and appetite. Currently, non-selective amylin and calcitonin receptor activators have been tested for body weight reduction to treat obesity. Here, multiple peptide activators for human amylin and calcitonin receptors were developed by introducing comprehensive mutagenesis to rat amylin peptide. The rat amylin peptide C-terminal fragment that interacts with amylin receptor extracellular domain was used to screen for affinity-enhancing mutations. Up to twelve mutational combinations were found to significantly increase peptide affinity both for amylin and calcitonin receptor extracellular domains by over 100-fold. Using these affinity-enhancing mutations, three representative rat amylin analogs with thirty-seven amino acids were made to test the potency increase for amylin and calcitonin receptor activation. All three mutated rat amylin analogs showed significant potency increases by 5- to 10-fold compared to endogenous rat amylin. These mutated peptide activators also showed higher potency for human amylin and calcitonin receptor activation than a clinically available amylin receptor activator pramlintide. These amylin and calcitonin receptor activators developed in this study may be useful as the valuable pharmacological tools that activate amylin receptors in cell-based systems.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"762 ","pages":"Article 110191"},"PeriodicalIF":3.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxalate-upregulated annexin A6 promotes the formation of calcium oxalate kidney stones by exacerbating calcium release-mediated oxidative stress injury in renal tubular epithelial cells and crystal-cell adhesion","authors":"Fei Xiao ,&nbsp;Yi Guan ,&nbsp;Ting Liu,&nbsp;Yan Zeng,&nbsp;Hengcheng Zhu,&nbsp;Kang Yang","doi":"10.1016/j.abb.2024.110187","DOIUrl":"10.1016/j.abb.2024.110187","url":null,"abstract":"<div><div>Kidney stones result from abnormal biomineralization, although the mechanism behind their formation remains unclear. Annexin A6 (AnxA6), a calcium-dependent lipid-binding protein, is associated with several mineralization-related diseases, but its role in kidney stones is unknown. This study aimed to explore the role and mechanism of AnxA6 in calcium oxalate (CaOx) kidney stones. An in vitro model in which renal tubular epithelial cells (RTECs) were treated with 1 mmol/L oxalate was established, and AnxA6 protein and mRNA expression were examined. Genetic engineering, drug intervention, and biochemical assays were used to investigate the role of AnxA6. The results revealed that AnxA6 was significantly overexpressed in the CaOx model. AnxA6 knockdown in RTECs reduced oxalate-induced oxidative stress, ROS accumulation, and mitochondrial damage, whereas AnxA6 overexpression exacerbated these effects. Blocking ryanodine receptor-mediated calcium release reversed AnxA6-induced oxidative damage. Additionally, AnxA6 increased oxalate adhesion to RTECs by binding to oxalate. In conclusion, AnxA6 contributes to CaOx kidney stone formation by promoting both oxidative stress via calcium release and crystal-cell adhesion by binding to oxalate. This study offers new insight into CaOx kidney stone formation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110187"},"PeriodicalIF":3.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142537857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of host autophagy in intracellular protozoan parasites diseases","authors":"Rafael Cardoso Maciel Costa Silva ,&nbsp;Jhones Sousa Ribeiro ,&nbsp;Thalita Santos de Moraes de Farias ,&nbsp;Leonardo Holanda Travassos","doi":"10.1016/j.abb.2024.110186","DOIUrl":"10.1016/j.abb.2024.110186","url":null,"abstract":"<div><div>Intracellular protozoan parasites are the etiologic agents of important human diseases, like malaria, Chagas disease, toxoplasmosis, and leishmaniasis. Inside host cells, these parasites manipulate the host metabolism and intracellular trafficking for their own benefits and, inevitably, induce several stress response mechanisms. In this review, we discuss autophagy as a stress response mechanism that can be both (i) explored by these intracellular parasites to acquire nutrients and (ii) to restrict parasite proliferation and survival within host cells. We also discuss the immunomodulatory role of autophagy as a strategy to reduce inflammatory-mediated damage, an essential player in the pathophysiology of these parasitic diseases. At last, we propose and discuss several known autophagy modulators as possible pharmaceuticals for adjunctive therapies.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110186"},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tackling APOE's structural challenges via in silico modeling in the era of neural networks: Can AlphaFold II help circumvent the problem of lacking full-length protein structure?","authors":"A.A. Mamchur ,&nbsp;M.V. Ivanov ,&nbsp;L.R. Matkava ,&nbsp;V.S. Yudin ,&nbsp;A.A. Keskinov ,&nbsp;S.M. Yudin ,&nbsp;D.A. Kashtanova","doi":"10.1016/j.abb.2024.110185","DOIUrl":"10.1016/j.abb.2024.110185","url":null,"abstract":"<div><div>The APOE gene, encoding apolipoprotein E, is a predictor of longevity and age-related diseases. Despite numerous genetic studies, the data on molecular mechanisms by which apolipoprotein E affects the human phenotype remain incomplete due to the structural properties of the protein. Recently, a number of studies have used in silico drug discovery techniques based on protein-ligand docking, further highlighting the issue of lacking 3D structure of apolipoprotein E. Using molecular dynamics simulation, we found that AlphaFold II models of apolipoprotein E conformationally significantly differ both from the only available NMR structure, 2L7B, and structures obtained through circular dichroism spectroscopy: the ε4 isoform lacks the salt bridge between R61 and E255, while the ε2 and ε3 isoforms have extensive networks of interdomain interactions. Our findings challenge the benefits of using AlphaFold II for obtaining starting conformations for molecular docking.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110185"},"PeriodicalIF":3.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation strongly affects the inhibition of human carbonic anhydrase I CO2 hydration activity","authors":"Andrea Angeli ,&nbsp;Vivian De Luca ,&nbsp;Xiaojing Huang ,&nbsp;Daniel L. Winter ,&nbsp;Clemente Capasso ,&nbsp;Claudiu T. Supuran ,&nbsp;William A. Donald","doi":"10.1016/j.abb.2024.110182","DOIUrl":"10.1016/j.abb.2024.110182","url":null,"abstract":"<div><div>Human carbonic anhydrases (hCAs) have essential roles in respiration, acid-base balance, and fluid secretion, with implications in diseases such as glaucoma, epilepsy, obesity, and cancer. Of the fifteen known hCAs, human CA I (hCA I) is particularly abundant in erythrocytes, playing a critical role in CO₂ transport. Despite extensive research on hCA I, the impact of post-translational modifications (PTMs), particularly phosphorylation, on its catalytic activity and inhibitor binding remains poorly understood. Although multiple phosphorylation sites have been identified in hCA I <em>in vivo</em> through high-throughput proteomics studies including at the highly conserved Ser51 residue, the functional consequences of these modifications are not well characterized. We investigated the effects of a phosphomimetic mutation at Ser51 on hCA I, examining its catalytic efficiency and susceptibility to inhibition by sulfonamides and anions. Using a recombinant expression system and a stopped-flow kinetic assay, we characterized the CO₂ hydration activity and inhibition profiles of S51E hCA I compared to the wild type enzyme. Our results demonstrate that the S51E mutation increases the catalytic turnover rate (<em>k</em>_cat) from 2.0 × 10⁵ s⁻¹ to 2.6 × 10⁵ s⁻¹ but significantly decreases substrate affinity, raising the Michaelis constant (<em>K</em>_M) from 4.0 mM to 13.9 mM, reducing overall catalytic efficiency by over 50 %. Inhibition studies with a panel of 41 sulfonamides revealed that the S51E mutation dramatically alters inhibitor sensitivity, particularly for the most effective inhibitors. For example, 15 of the 16 most effective sulfonamide inhibitors for hCA I (with <em>K</em>_Is &lt;350 nM) were an average of over 35-fold less effective in inhibiting S51E hCA I than the wild type. The <em>K</em>_I of the anticonvulsant zonisamide increased from 31 nM for the wild type hCA I to 4.0 μM. The inhibition profile with a panel of 37 small anions further indicated that the S51E mutant exhibited significantly reduced susceptibility to inhibition by 24 out of 37 tested anions, with some <em>K</em>_I values increasing by up to 11,000-fold for inhibitors like hydrogen sulfide. This study underscores the significant impact that phosphorylation may have on hCA I function and inhibition. By characterizing the effects of phosphorylation on the CO₂ hydration activity and inhibitor sensitivity of hCA I, these findings represent early steps in developing more selective proteoform-specific inhibitors, which could lead to more effective treatments for diseases involving carbonic anhydrases.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110182"},"PeriodicalIF":3.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445697","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":"FYCO1 regulates autophagy and senescence via PAK1/p21 in cataract","authors":"Shuying Chen ,&nbsp;Wei Zhao ,&nbsp;Rongrong Chen ,&nbsp;Feiyin Sheng ,&nbsp;Yuzhou Gu ,&nbsp;Shengjie Hao ,&nbsp;Di Wu ,&nbsp;Bing Lu ,&nbsp;Lu Chen ,&nbsp;Yuhao Wu ,&nbsp;Yili Xu ,&nbsp;Yu Han ,&nbsp;Lei Zhou ,&nbsp;S. Amer Riazuddin ,&nbsp;Qiuli Fu ,&nbsp;Ke Yao","doi":"10.1016/j.abb.2024.110180","DOIUrl":"10.1016/j.abb.2024.110180","url":null,"abstract":"<div><h3>Background</h3><div>ARC (Age-related cataract<strong>)</strong> is one of the leading causes of vision impairment and blindness; however, its pathogenesis remains unclear. FYCO1 (FYVE and coiled-coil domain containing 1) serves as an autophagy adaptor. The present study investigated the role of FYCO1 in cataract.</div></div><div><h3>Methods</h3><div>Ultraviolet-B (UVB) irradiation was used to establish a cataract mice model. Hematoxylin and eosin (H&amp;E) assay were used to observe lens morphology. Cell models were constructed by cultivating SRA 01/04 cells with H₂O₂ and UVB. Cell counting kit-8 (CCK8) and Senescence-associated β-galactosidase (SA-β-Gal) assay were performed to explore proliferation and senescence. The gene and protein expression were assessed by quantitative real-time PCR (qRT-PCR), Western blot and immunofluorescence staining.</div></div><div><h3>Results</h3><div>We demonstrated lens structural damage and downregulation of FYCO1 in mice with UVB-induced cataracts. <em>In vitro</em> results revealed a deletion in autophagy levels along with the decrease of <em>FYCO1</em> expression in human lens epithelial cells (HLECs) after H₂O₂ treatment, which was confirmed <em>in vivo</em>. The knockout of <em>FYCO1</em> in the HLECs did not change basal autophagy and senescence but suppressed HLECs response in the induction of both. Further investigation indicated that <em>FYCO1</em> knockout inhibited senescence and p21 levels by suppressing the expression of p21 activated kinase 1 (PAK1) in cataract cell models.</div></div><div><h3>Conclusions</h3><div>This study has newly characterized the role of FYCO1 in UVB-induced cataracts and in oxidative stress, both of which are associated with ARCs. A novel association between FYCO1 and PAK1/p21 in lens epithelial cell autophagy, senescence, and cataractogenesis also appears to have been established.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110180"},"PeriodicalIF":3.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of novel 1,3-diaryltriazene-sulfamethazines with carbonic anhydrases: Kinetic studies and in silico simulations","authors":"Nabih Lolak ,&nbsp;Cüneyt Türkeş ,&nbsp;Suleyman Akocak ,&nbsp;Hatice Esra Duran ,&nbsp;Mesut Işık ,&nbsp;Mustafa Durgun ,&nbsp;Şükrü Beydemir","doi":"10.1016/j.abb.2024.110181","DOIUrl":"10.1016/j.abb.2024.110181","url":null,"abstract":"<div><div>Sulfonamides, recognized as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, are crucial in treating diverse diseases, including epilepsy, glaucoma, bacterial infections, and various pathological processes, e.g., high blood pressure, rheumatoid arthritis, ulcerative colitis, pain, and inflammation. Additionally, therapeutically, 1,3-diaryl-substituted triazenes and sulphamethazines (<strong>SM</strong>) are integral components in various drug structures, and the synthesis of novel compounds within these two categories holds substantial significance. Herein, ten 1,3-diaryltriazene-substituted sulphamethazine derivatives <strong>SM(1</strong>–<strong>10)</strong>, which were created by reacting the diazonium salt of sulphamethazine with substituted aromatic amines, were synthesized and the physiologically and pharmacologically relevant human (<em>h</em>) isoforms <em>h</em>CA I and II, cytosolic isozymes, were included in the study. The synthesized compounds showed excellent inhibition versus <em>h</em>CAs; the 4-butoxy (<strong>SM7</strong>, <em>K</em>_I of 5.69 ± 0.59 nM) compound exhibited a potent inhibitory effect against the <em>h</em>CA I compared with the reference drug acetazolamide (AAZ, <em>K</em>_I of 116.00 ± 8.48 nM). The 4-cyano (<strong>SM4</strong>, <em>K</em>_I of 5.87 ± 0.57 nM) compound displayed higher potency than AAZ (<em>K</em>_I of 57.25 ± 4.15 nM) towards <em>h</em>CA II. Meanwhile, among the synthesized molecules, the 3,4-dimethoxy (<strong>SM9</strong>, <em>K</em>_I of 74.98 ± 10.49 nM, <em>S</em>_I of 9.94) compound (over <em>h</em>CA I) displayed a noticeable selectivity for <em>h</em>CA isoform II. The target compounds in the molecular docking investigation were determined to take part in various hydrophilic and hydrophobic interactions with nearby amino acids and fit nicely into the active sites of the <em>h</em>CAs. This research has yielded compounds displaying varying affinity toward <em>h</em>CA isoenzymes, ultimately serving as potent and selective <em>h</em>CA inhibitors. Given its substantial biological inhibitory potency, this particular derivative series is determined to hold the potential to serve as a promising lead compound against these <em>h</em>CAs.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110181"},"PeriodicalIF":3.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical aggregation concentration and reversibility of amyloid-β (1–40) oligomers","authors":"Sara Illodo ,&nbsp;Wajih Al-Soufi ,&nbsp;Mercedes Novo","doi":"10.1016/j.abb.2024.110179","DOIUrl":"10.1016/j.abb.2024.110179","url":null,"abstract":"<div><div>Amyloid-beta (Aβ) aggregation is a critical factor in the pathogenesis of Alzheimer's disease, with distinct aggregation behaviours observed between its isoforms Amyloid-β 1–40 (Aβ40) and 1–42 (Aβ42). In this study, we investigated the aggregation properties of Aβ40 using fluorescence correlation spectroscopy (FCS) and detailed data analysis. Our results reveal that Aβ40 undergoes a two-step cooperative aggregation process. The first step, characterized by a critical aggregation concentration (<em>cac</em>) of 0.5 ± 0.3 μM, results in the formation of metastable oligomers of 5–25 monomers and stable oligomers of 50–100 monomers, with less than 10 % of the total amyloid aggregated. The second step, with a <em>cac</em> of 19 ± 2 μM, leads to the formation of much larger aggregates, consistent with protofibrils, and approximately 50 % aggregated amyloid. Notably, the <em>cac</em> for Aβ40 is significantly higher, and the fraction of aggregated amyloid is much lower compared to Aβ42, indicating a lower propensity for aggregation. Additionally, our findings suggest that Aβ40 early oligomers are reversible upon dilution, albeit with a kinetic barrier to disaggregation. These insights into the aggregation mechanisms of Aβ40 enhance our understanding of its role in Alzheimer's disease and may inform therapeutic strategies targeting amyloid aggregation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110179"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405963","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":"Searching for the role of membrane lipids in the mechanism of antibacterial effect of hinokitiol","authors":"Beata Wyżga ,&nbsp;Magdalena Skóra ,&nbsp;Karolina Olechowska ,&nbsp;Marcin Broniatowski ,&nbsp;Paweł Wydro ,&nbsp;Katarzyna Hąc-Wydro","doi":"10.1016/j.abb.2024.110178","DOIUrl":"10.1016/j.abb.2024.110178","url":null,"abstract":"<div><div>The aim of this work was to investigate the effect of monoterpenoid hinokitiol (β-thujaplicin) on the monolayers and bilayers composed of lipids typical for bacteria membranes and gain insight into the potential role of the lipids in antibacterial activity and selectivity of this compound. To explore this issue, the <em>in vitro</em> studies were performed on different bacterial strains to verify antibacterial potency of hinokitiol. Then, the experiments on <em>E. coli</em> and <em>S. aureus</em> bacteria membrane models (i.e. model multicomponent monolayers and bilayers) were done. Finally, the effect of hinokitiol on one component lipid monolayers was investigated. The lipids used in the experiments included Phosphatidylethanolamines (PEs), Phosphatidylglycerols (PGs) and Cardiolipins differing in the structure of the polar head and/or the hydrophobic chains. This choice allowed the analysis of correlations between the lipid structure and the effect of hinokitiol.</div><div><em>In vitro</em> tests confirmed the antimicrobial activity of hinokitiol against most of the strains tested. In addition, the <em>in vitro</em> tests showed that <em>E. coli</em> bacteria were more sensitive to hinokitiol than <em>S. aureus</em> bacteria. Interestingly, the studies on model systems evidenced that hinokitiol molecules are of stronger effect on <em>E.coli</em> film and they are able to insert into these systems even at membrane-related surface pressures. Moreover, the structure of the lipid and its content in the model system correlated with the effect exerted by hinokitiol on the monolayer properties. It was found that hinokitiol differs in the affinity to particular lipids and additionally hinokitiol/lipid interactions may occur according to different mechanisms. Namely, depending on the lipid structure, hinokitiol may incorporate into the lipid film (Cardiolipins and PEs) or interact preferentially with the lipid polar head (PGs) and form hydrogen bonds. The effect of hinokitiol on the lipids was determined by the charge and size of the polar head as well as by the spatial size of the lipid molecule. Moreover, comparing the lipids of the same polar heads, hinokitiol caused stronger expansion of the film formed from the lipid having unsaturated chains. The results obtained may explain the difference in the effect of hinokitiol on particular bacterial strains. In conclusions, it can be suggested that the lipids should be considered as the bacteria membrane structural elements of a possible role in the mechanism of action of hinokitiol.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110178"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405966","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}