Archives of biochemistry and biophysics最新文献

{"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}

{"title":"Folic acid-functionalized and acetyl-terminated dendrimers as nanovectors for co-delivery of sorafenib and 5-fluorouracil","authors":"Ali Hussein Mezher,&nbsp;Mahboobeh Salehpour,&nbsp;Zohreh Saadati","doi":"10.1016/j.abb.2024.110176","DOIUrl":"10.1016/j.abb.2024.110176","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Molecular dynamics (MD) simulations were employed to investigate the simultaneous association of sorafenib (SF) and 5-fluorouracil (5-FU) with generation 4 (G4) acetyl-terminated poly(amidoamine) (PAMAM) dendrimers conjugated with folic acid (G4ACE-FA). Simulations were conducted under physiological (pH 7.4) and acidic (pH &lt; 5) conditions, representing the environments of healthy and cancerous cells, respectively. The average radius of gyration (&lt;em&gt;R&lt;/em&gt;&lt;sub&gt;g&lt;/sub&gt;) of G4ACE-FA was determined to be approximately 1.85 ± 0.01 nm and 2.31 ± 0.03 nm under physiological and acidic conditions, respectively. Drug loading did not exert a significant influence on the size and conformational compactness of G4ACE-FA at both neutral and low pH. However, a discernible increase in dendrimer size was observed upon simultaneous encapsulation and/or conjugation of both drug molecules. The relaxation times of G4ACE-FA were calculated to be 10.2 ns and 9.6 ns at neutral and low pH, respectively, indicating comparable equilibrium rates under both pH environments. The incorporation of small 5-FU molecules did not demonstrably alter the dendrimer's microstructure. The observed doubling of the relaxation time under acidic conditions can be attributed to the relatively compact structure of the dendrimer at neutral pH and the continuous intrastructural rearrangements occurring at acidic pH. The prolonged relaxation time observed in the G4ACE-FA:5-FU:SF complex is attributed to competitive interactions between 5-FU and SF molecules during simultaneous encapsulation by the dendrimer. Analysis of the unloaded and loaded structures of G4ACE-FA under varying pH conditions revealed a densely packed conformation at neutral pH and a more open, sponge-like structure at low pH. The solvent-accessible surface area (SASA) of the dendrimer was assessed at both pH conditions. At neutral pH, SASA values were approximately 124.0 ± 2.8 nm&lt;sup&gt;2&lt;/sup&gt;, 127.5 ± 2.6 nm&lt;sup&gt;2&lt;/sup&gt;, 131.3 ± 2.6 nm&lt;sup&gt;2&lt;/sup&gt;, and 133.3 ± 2.6 nm&lt;sup&gt;2&lt;/sup&gt; for unloaded G4ACE-FA and the G4ACE-FA:5-FU, G4ACE-FA:SF, and G4ACE-FA:5-FU:SF complexes, respectively. Drug incorporation had a minimal effect on SASA at neutral pH. At low pH, the corresponding values were 198.2 ± 4.7 nm&lt;sup&gt;2&lt;/sup&gt;, 195.8 ± 4.8 nm&lt;sup&gt;2&lt;/sup&gt;, 212.5 ± 6.1 nm&lt;sup&gt;2&lt;/sup&gt;, and 215.4 ± 4.2 nm&lt;sup&gt;2&lt;/sup&gt;. These findings suggest that 5-FU encapsulation resulted in minimal changes to the dendrimer's surface exposure to the solvent, potentially due to its small size. In contrast, SF interaction led to a more pronounced increase in SASA, indicating structural expansion to accommodate SF conjugation. The equilibrium stoichiometry of the G4ACE-FA:5-FU complex was determined to be 1:11 and 1:3 at neutral and low pH, respectively. Similarly, the G4ACE-FA:SF complex exhibited equilibrium stoichiometries of 1:10 and 1:4 at neutral and low pH. The G4ACE-FA:5-FU:SF complex displayed stoichiometries of 1:11:10 at neutral pH and 1:3:3 a","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"762 ","pages":"Article 110176"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405964","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":"New Advances in Understanding Inhibition of Myeloperoxidase and Neutrophil Serine Proteases by Two Families of Staphylococcal Innate Immune Evasion Proteins","authors":"Timothy J. Herdendorf ,&nbsp;Nitin Mishra ,&nbsp;Soheila Fatehi ,&nbsp;Carson D. Gido,&nbsp;Om Prakash,&nbsp;Brian V. Geisbrecht","doi":"10.1016/j.abb.2024.110177","DOIUrl":"10.1016/j.abb.2024.110177","url":null,"abstract":"<div><div>Neutrophils are the most abundant leukocytes in humans and play an important early role in the innate immune response against microorganisms. Neutrophil phagosomes contain high concentrations of antibacterial enzymes, including myeloperoxidase (MPO) and the neutrophil serine proteases (NSPs). These antibacterial enzymes can also be released extracellularly upon degranulation or as a component of neutrophil extracellular traps (NETs). Due to host/pathogen coevolution, <em>S. aureus</em> expresses a diverse arsenal of innate immune evasion proteins that target many aspects of the neutrophil antibacterial response. In the last decade, two new classes of staphylococcal innate immune evasion proteins that act as potent, selective inhibitors of MPO and NSPs, respectively, have been discovered. The Staphylococcal Peroxidase INhibitor (SPIN) is a small ∼8.3 kDa α-helical bundle protein that blocks MPO activity by interfering with substrate and product exchange with the MPO active site. The Extracellular Adherence Protein (EAP) family consists of three unique proteins comprised of one or more copies of an ∼11 kDa β-grasp domain capable of high-affinity, selective, non-covalent inhibition of NSPs. This brief review article summarizes recent advances in understanding the structural and functional properties of SPIN and EAP family members and outlines some potential avenues for future investigation of these enzyme inhibitors.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110177"},"PeriodicalIF":3.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405965","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 LncRNA6524/miR-92a-2-5p/Dvl1/Wnt/β-catenin axis promotes renal fibrosis in the UUO mouse model","authors":"Yuxin Xie ,&nbsp;Guoxiu Zhang ,&nbsp;Jian Pan ,&nbsp;Shuangfa Qiu ,&nbsp;Dongshan Zhang","doi":"10.1016/j.abb.2024.110175","DOIUrl":"10.1016/j.abb.2024.110175","url":null,"abstract":"<div><div>LncRNAs are reported to participate in multiple biological and pathological processes, including renal fibrosis due to obstructive nephropathy. However, the function and mechanisms of each lncRNA in this context differ. In this study, we created a fibrosis model in vitro using TGF-β1 treatment and in vivo through unilateral ureteral obstruction. We demonstrated that lncRNA6524 expression increased in both models, as confirmed by qPCR. Additionally, we discovered that lncRNA6524 mediates the TGF-β1-induced accumulation of extracellular matrix (ECM) proteins in BUMPT cells. We investigated the mechanism using dual luciferase reporter assays, immunofluorescence, and qPCR. Our results indicate that lncRNA6524 acts as a sponge for miR-92a-2-5p, promoting renal fibrosis by upregulating the Dvl1/Wnt/β-catenin signaling pathway. In summary, our findings demonstrate a linear regulatory relationship among lncRNA6524, miR-92a-2-5p, and the Dvl1/Wnt/β-catenin axis in renal epithelial cells during kidney obstruction. This highlights a new potential target for treating obstruction-related renal fibrosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"761 ","pages":"Article 110175"},"PeriodicalIF":3.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399204","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}