Biochimie最新文献

{"title":"Myelin basic protein antagonizes the SARS-CoV-2 protein ORF3a-induced autophagy inhibition","authors":"George A. Saratov ,&nbsp;Alexey A. Belogurov Jr. ,&nbsp;Anna A. Kudriaeva","doi":"10.1016/j.biochi.2024.04.011","DOIUrl":"10.1016/j.biochi.2024.04.011","url":null,"abstract":"<div><p>Inhibition of autophagy is one of the hallmarks of the SARS-CoV-2 infection. Recently it was reported that SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes via interaction with VPS39 thus preventing binding of homotypic fusion and protein sorting (HOPS) complex to RAB7 GTPase. Here we report that myelin basic protein (MBP), a major structural component of the myelin sheath, binds ORF3a and is colocalized with it in mammalian cells. Co-expression of MBP with ORF3a restores autophagy in mammalian cells, inhibited by viral protein. Our data suggest that basic charge of MBP drives suppression of ORF3a-induced autophagy inhibition as its deaminated variants lost ability to bind ORF3a and counteract autophagy blockade. These results together with our recent findings, indicating that MBP interacts with structural components of the vesicle transport machinery-synaptosomal-associated protein 23 (SNAP23), vesicle-associated membrane protein 3 (VAMP3) and Sec1/Munc18-1 family members, may suggest protective role of the MBP in terms of the maintaining of protein traffic and autophagosome–lysosome fusion machinery in oligodendrocytes during SARS-CoV-2 infection. Finally, our data may indicate that deimination of MBP observed in the patients with multiple sclerosis (MS) may contribute to the previously reported worser outcomes of COVID-19 and increase of post-COVID-19 neurologic symptoms in patients with MS.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"225 ","pages":"Pages 1-9"},"PeriodicalIF":3.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862503","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":"A U2 snRNP-specific protein, U2A′, is involved in stress response and drug resistance in Cryptococcus deneoformans","authors":"Lan Ma ,&nbsp;Xueqing Zhang ,&nbsp;Chenxi Li ,&nbsp;Xiaoyu Ma ,&nbsp;Xuan Zhao ,&nbsp;Xueru Zhao ,&nbsp;Ping Zhang ,&nbsp;Xudong Zhu","doi":"10.1016/j.biochi.2023.10.005","DOIUrl":"10.1016/j.biochi.2023.10.005","url":null,"abstract":"<div><p><span>The spliceosome<span><span>, a large complex containing five conserved small ribonucleoprotein particles (snRNPs) U1, U2, U4, U5 and U6, plays important roles in precursor messenger </span>RNA splicing. However, the function and mechanism of the spliceosomal snRNPs have not been thoroughly studied in the pathogenic yeast </span></span><span><em>Cryptococcus</em><em> deneoformans</em></span>. In this study, we identified a U2A′ homologous protein as a component of the cryptococcal U2 snRNP, which was encoded by the <em>LEA1</em> gene. Using the “suicide” CRISPR-Cas9 tool, we deleted the <em>LEA1</em> gene in <em>C. deneoformans</em> JEC21 strain and obtained the disruption mutant <em>lea1</em><span>Δ. The mutant showed a hypersensitivity to 0.03 % sodium dodecyl sulfate<span>, as well as disordered chitin distribution in cell wall observed with Calcofluor White staining, which collectively illustrated the function of U2A′ in maintenance of cell wall integrity. Further examination showed that </span></span><em>lea1</em><span>Δ displayed a decreased tolerance to lower or elevated temperatures, osmotic pressure<span> and oxidative stress. The </span></span><em>lea1</em>Δ still exhibited susceptibility to geneticin and 5-flucytosine, and increased resistance to ketoconazole. Even, the mutant had a reduced capsule, and the virulence of <em>lea1</em>Δ in the <span><em>Galleria mellonella</em></span> model was decreased. Our results indicate that the U2A′-mediated RNA-processing has a particular role in the processing of gene products involved in response to stresses and virulence.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"220 ","pages":"Pages 179-187"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165315","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":"Inside front cover-EDB","authors":"","doi":"10.1016/S0300-9084(24)00087-7","DOIUrl":"https://doi.org/10.1016/S0300-9084(24)00087-7","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"220 ","pages":"Page IFC"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000877/pdfft?md5=9b7bd9bb9ddd184f10170b2b2b308355&pid=1-s2.0-S0300908424000877-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843105","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":"Mesenchymal stem cells in autoimmune disease: A systematic review and meta-analysis of pre-clinical studies","authors":"Hailey N. Swain ,&nbsp;Parker D. Boyce ,&nbsp;Bradley A. Bromet ,&nbsp;Kaiden Barozinksy ,&nbsp;Lacy Hance ,&nbsp;Dakota Shields ,&nbsp;Gayla R. Olbricht ,&nbsp;Julie A. Semon","doi":"10.1016/j.biochi.2024.04.009","DOIUrl":"10.1016/j.biochi.2024.04.009","url":null,"abstract":"<div><p>Mesenchymal Stem Cells (MSCs) are of interest in the clinic because of their immunomodulation capabilities, capacity to act upstream of inflammation, and ability to sense metabolic environments. In standard physiologic conditions, they play a role in maintaining the homeostasis of tissues and organs; however, there is evidence that they can contribute to some autoimmune diseases. Gaining a deeper understanding of the factors that transition MSCs from their physiological function to a pathological role in their native environment, and elucidating mechanisms that reduce their therapeutic relevance in regenerative medicine, is essential. We conducted a Systematic Review and Meta-Analysis of human MSCs in preclinical studies of autoimmune disease, evaluating 60 studies that included 845 patient samples and 571 control samples. MSCs from any tissue source were included, and the study was limited to four autoimmune diseases: multiple sclerosis, rheumatoid arthritis, systemic sclerosis, and lupus. We developed a novel Risk of Bias tool to determine study quality for <em>in vitro</em> studies. Using the International Society for Cell &amp; Gene Therapy's criteria to define an MSC, most studies reported no difference in morphology, adhesion, cell surface markers, or differentiation into bone, fat, or cartilage when comparing control and autoimmune MSCs. However, there were reported differences in proliferation. Additionally, 308 biomolecules were differentially expressed, and the abilities to migrate, invade, and form capillaries were decreased. The findings from this study could help to explain the pathogenic mechanisms of autoimmune disease and potentially lead to improved MSC-based therapeutic applications.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 54-73"},"PeriodicalIF":3.9,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140783091","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":"Enhanced structure/function of mTSPO translocator in lipid:surfactant mixed micelles","authors":"","doi":"10.1016/j.biochi.2024.04.008","DOIUrl":"10.1016/j.biochi.2024.04.008","url":null,"abstract":"<div><p>TSPO is a ubiquitous transmembrane protein used as a pharmacological marker in neuroimaging. The only known atomic structure of mammalian TSPOs comes from the solution NMR of mouse TSPO (mTSPO) bound to the PK11195 ligand and in a DPC surfactant environment. No structure is available in a biomimetic environment and without PK11195 which strongly stiffens the protein.</p><p>We measured the effect of different amphiphilic environments on ligand-free mTSPO to study its structure/function and find optimal solubilization conditions. By replacing the SDS surfactant, where the recombinant protein is purified, with mixed lipid:surfactant (DMPC:DPC) micelles at different ratios (0:1, 1:2, and 2:1, <em>w</em>:<em>w</em>), the α-helix content and interactions and the intrinsic tryptophan (Trp) fluorescence of mTSPO are gradually increased.</p><p>Small-angle X-ray scattering (SAXS) shows a more extended mTSPO/belt complex with the addition of lipids: <em>D</em>_max ∼95 Å in DPC alone <em>versus</em> ∼142 Å in DMPC:DPC (1:2). SEC-MALLS shows that the molecular composition of the mTSPO belt is ∼98 molecules for DPC alone and ∼58 DMPC and ∼175 DPC for DMPC:DPC (1:2). Additionally, DMPC:DPC micelles stabilize mTSPO compared to DPC alone, where the protein has a greater propensity to aggregate. These structural changes are consistent with the increased affinity of mTSPO for the PK11195 ligand in presence of lipids (<em>K</em>_d ∼70 μM in DPC alone <em>versus</em> ∼0.91 μM in DMPC:DPC, 1:2), as measured by microscale thermophoresis (MST).</p><p>In conclusion, mixed lipid:surfactant micelles open new possibilities for the stabilization of membrane proteins and for their study in solution in a more biomimetic amphiphilic environment.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"224 ","pages":"Pages 3-15"},"PeriodicalIF":3.3,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030090842400083X/pdfft?md5=9e427a6cb180bd19b969cc361f24fb0b&pid=1-s2.0-S030090842400083X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140759850","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":"Effect of metformin in hypothalamic astrocytes from an immunocompromised mice model","authors":"Larissa Daniele Bobermin ,&nbsp;Daniele Schauren da Costa ,&nbsp;Aline Daniel Moreira de Moraes ,&nbsp;Vanessa Fernanda da Silva ,&nbsp;Giancarlo Tomazzoni de Oliveira ,&nbsp;Patrícia Sesterheim ,&nbsp;Ana Carolina Tramontina ,&nbsp;Luiz Augusto Basso ,&nbsp;Guilhian Leipnitz ,&nbsp;André Quincozes-Santos ,&nbsp;Carlos-Alberto Gonçalves","doi":"10.1016/j.biochi.2024.04.005","DOIUrl":"10.1016/j.biochi.2024.04.005","url":null,"abstract":"<div><p>Astrocytes are glial cells that play key roles in neuroinflammation, which is a common feature in diabetic encephalopathy and aging process. Metformin is an antidiabetic compound that shows neuroprotective properties, including in inflammatory models, but astroglial signaling pathways involved are still poorly known. Interferons α/β are cytokines that participate in antiviral responses and the lack of their signaling increases susceptible to viral infections. Here, we investigated the effects of metformin on astrocytes from hypothalamus, a crucial brain region related to inflammatory processes. Astrocyte cultures were derived from interferon α/β receptor knockout (IFNα/βR^−/−) and wild-type (WT) mice. Metformin did not change the expression of glial fibrillary acidic protein but caused an anti-inflammatory effect by decreasing pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), as well as increasing gene expression of anti-inflammatory proteins interleukin-10 and Nrf2 (nuclear factor erythroid derived 2 like 2). However, nuclear factor κB p65 and cyclooxygenase 2 were downregulated in WT astrocytes and upregulated in IFNα/βR^−/− astrocytes. AMP-activated protein kinase (AMPK), a molecular target of metformin, was upregulated only in WT astrocytes, while sirtuin 1 increased in both mice models. The expression of inducible nitric oxide synthase was decreased in WT astrocytes and heme oxygenase 1 was increased in IFNα/βR^−/− astrocytes. Although loss of IFNα/βR-mediated signaling affects some effects of metformin, our results support beneficial roles of this drug in hypothalamic astrocytes. Moreover, paradoxical response of metformin may involve AMPK. Thus, metformin can mediate glioprotection due its effects on age-related disorders in non-diabetic and diabetic encephalopathy individuals.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 196-205"},"PeriodicalIF":3.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760219","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":"CpG methylation changes in human mesenchymal and neural stem cells in response to in vitro niche modifications","authors":"Martina Gyimesi ,&nbsp;Lotta E. Oikari ,&nbsp;Chieh Yu ,&nbsp;Heidi G. Sutherland ,&nbsp;Dale R. Nyholt ,&nbsp;Lyn R. Griffiths ,&nbsp;Andre J. Van Wijnen ,&nbsp;Rachel K. Okolicsanyi ,&nbsp;Larisa M. Haupt","doi":"10.1016/j.biochi.2024.04.007","DOIUrl":"10.1016/j.biochi.2024.04.007","url":null,"abstract":"<div><p>Stem cell therapies hold promise in addressing the burden of neurodegenerative diseases with human embryonic neural stem cells (hNSC-H9s) and bone marrow-derived human mesenchymal stem cells (hMSCs) as viable candidates. The induction of hMSC neurospheres (hMSC-IN) generate a more lineage-restricted common neural progenitor-like cell population, potentially tunable by heparan sulfate proteoglycans (HSPGs). We examined CpG (5 mC) site methylation patterns using Illumina Infinium 850 K EPIC arrays in hNSC-H9, hMSCs and hMSC-IN cultures with HSPG agonist heparin at early and late phases of growth. We identified key regulatory CpG sites in syndecans (<em>SDC2; SDC4</em>) that potentially regulate gene expression in monolayers. Unique hMSC-IN hypomethylation in glypicans (<em>GPC3</em>; <em>GPC4)</em> underscore their significance in neural lineages with Sulfatase 1 and 2 (<em>SULF1</em> &amp; <em>2</em>) CpG methylation changes potentially driving the neurogenic shift. hMSC-INs methylation levels at <em>SULF1</em> CpG sites and <em>SULF2</em>:cg25401628 were more closely aligned with hNSC-H9 cells than with hMSCs. We further suggest <em>SOX2</em> regulation governed by lncSOX2-Overall Transcript <em>(lncSOX2-OT)</em> methylation changes with preferential activation of <em>ENO2</em> over other neuronal markers within hMSC-INs. Our findings illuminate epigenetic dynamics governing neural lineage commitment of hMSC-INs offering insights for targeted mechanisms for regenerative medicine and therapeutic strategies.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 147-157"},"PeriodicalIF":3.3,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000828/pdfft?md5=1d288c983293875ff2a9342fcffc1843&pid=1-s2.0-S0300908424000828-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140793340","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":"NADPH oxidase-generated reactive oxygen species are involved in estradiol 17ß-d-glucuronide-induced cholestasis","authors":"Gimena Salas,&nbsp;Alen A. Litta,&nbsp;Anabela C. Medeot,&nbsp;Virginia S. Schuck,&nbsp;Romina B. Andermatten,&nbsp;Gisel S. Miszczuk,&nbsp;Nadia Ciriaci,&nbsp;Ma Valeria Razori,&nbsp;Ismael R. Barosso,&nbsp;Enrique J. Sánchez Pozzi,&nbsp;Marcelo G. Roma,&nbsp;Cecilia L. Basiglio,&nbsp;Fernando A. Crocenzi","doi":"10.1016/j.biochi.2024.04.002","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.04.002","url":null,"abstract":"<div><p>The endogenous metabolite of estradiol, estradiol 17β-D-glucuronide (E17G), is considered the main responsible of the intrahepatic cholestasis of pregnancy. E17G alters the activity of canalicular transporters through a signaling pathway-dependent cellular internalization, phenomenon that was attributed to oxidative stress in different cholestatic conditions. However, there are no reports involving oxidative stress in E17G-induced cholestasis, representing this the aim of our work. Using polarized hepatocyte cultures, we showed that antioxidant compounds prevented E17G-induced Mrp2 activity alteration, being this alteration equally prevented by the NADPH oxidase (NOX) inhibitor apocynin. The model antioxidant <em>N</em>-acetyl-cysteine prevented, in isolated and perfused rat livers, E17G-induced impairment of bile flow and Mrp2 activity, thus confirming the participation of reactive oxygen species (ROS) in this cholestasis. In primary cultured hepatocytes, pretreatment with specific inhibitors of ERK1/2 and p38MAPK impeded E17G-induced ROS production; contrarily, NOX inhibition did not affect ERK1/2 and p38MAPK phosphorylation. Both, knockdown of p47phox by siRNA and preincubation with apocynin in sandwich-cultured rat hepatocytes significantly prevented E17G-induced internalization of Mrp2, suggesting a crucial role for NOX in this phenomenon. Concluding, E17G-induced cholestasis is partially mediated by NOX-generated ROS through internalization of canalicular transporters like Mrp2, being ERK1/2 and p38MAPK necessary for NOX activation.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 41-53"},"PeriodicalIF":3.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140555269","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":"Galactokinase-like protein from Leishmania donovani: Biochemical and structural characterization of a recombinant protein","authors":"Hasana Baber ,&nbsp;Arega Aghajani ,&nbsp;B. Harold Gallimore ,&nbsp;Cassandra Bethel ,&nbsp;James G. Hyatt ,&nbsp;Elizabeth F.B. King ,&nbsp;Helen P. Price ,&nbsp;Marissa L. Maciej-Hulme ,&nbsp;Suat Sari ,&nbsp;Anja Winter","doi":"10.1016/j.biochi.2024.03.017","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.03.017","url":null,"abstract":"<div><p>Leishmaniasis is a spectrum of conditions caused by infection with the protozoan <em>Leishmania</em> spp. parasites. Leishmaniasis is endemic in 98 countries around the world, and resistance to current anti-leishmanial drugs is rising. Our work has identified and characterised a previously unstudied galactokinase-like protein (GalK) in <em>Leishmania donovani</em>, which catalyses the MgATP-dependent phosphorylation of the C-1 hydroxyl group of <span>d</span>-galactose to galactose-1-phosphate. Here, we report the production of the catalytically active recombinant protein in <em>E. coli</em>, determination of its substrate specificity and kinetic constants, as well as analysis of its molecular envelope using <em>in solution</em> X-ray scattering. Our results reveal kinetic parameters in range with other galactokinases with an average apparent Km value of 76 μM for galactose, V_max and apparent K_cat values with 4.46376 × 10⁻⁹ M/s and 0.021 s⁻¹, respectively. Substantial substrate promiscuity was observed, with galactose being the preferred substrate, followed by mannose, fructose and GalNAc. <em>Ld</em>GalK has a highly flexible protein structure suggestive of multiple conformational states in solution, which may be the key to its substrate promiscuity. Our data presents novel insights into the galactose salvaging pathway in <em>Leishmania</em> and positions this protein as a potential target for the development of pharmaceuticals seeking to interfere with parasite substrate metabolism.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 31-40"},"PeriodicalIF":3.9,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140536810","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":"Multifunctional host-defense peptides isolated from skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae)","authors":"J. Michael Conlon ,&nbsp;Ananyaa Sridhar ,&nbsp;Dawood Khan ,&nbsp;Taylor S. Cunning ,&nbsp;Jack J. Delaney ,&nbsp;Megan G. Taggart ,&nbsp;Nigel G. Ternan ,&nbsp;Jérôme Leprince ,&nbsp;Laurent Coquet ,&nbsp;Thierry Jouenne ,&nbsp;Samir Attoub ,&nbsp;Milena Mechkarska","doi":"10.1016/j.biochi.2024.03.012","DOIUrl":"10.1016/j.biochi.2024.03.012","url":null,"abstract":"<div><p>Five host-defense peptides (figainin 2PL, hylin PL, raniseptin PL, plasticin PL, and peptide YL) were isolated from norepinephrine-stimulated skin secretions of the banana tree dwelling frog <em>Boana platanera</em> (Hylidae; Hylinae) collected in Trinidad.</p><p>Raniseptin PL (GVFDTVKKIGKAVGKFALGVAKNYLNS.NH₂) and figainin 2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ. NH₂) showed potent and rapid bactericidal activity against a range of clinically relevant Gram-positive and Gram-negative ESKAPE ⁺ pathogens and <em>Clostridioides difficile.</em> The peptides also showed potent cytotoxic activity (LC₅₀ values &lt; 30 μM) against A549, MDA-MB-231 and HT29 human tumor-derived cell lines but appreciably lower hemolytic activity against mouse erythrocytes (LC₅₀ = 262 ± 14 μM for raniseptin PL and 157 ± 16 μM for figainin 2PL). Hylin PL (FLGLIPALAGAIGNLIK.NH₂) showed relatively weak activity against microorganisms but was more hemolytic. The glycine-leucine-rich peptide with structural similarity to the plasticins (GLLSTVGGLVGGLLNNLGL.NH₂) and the non-cytotoxic peptide YL (YVPGVIESLL.NH₂) lacked antimicrobial and cytotoxic activities. Hylin PL, raniseptinPL and peptide YL stimulated the rate of release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥100 nM. Peptide YL was the most effective (2.3-fold increase compared with basal rate at 1 μM concentration) and may represent a template for the design of a new class of incretin-based anti-diabetic drugs.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 23-30"},"PeriodicalIF":3.9,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000701/pdfft?md5=0e62b58f0bacba03f8bb7c5ea584abbd&pid=1-s2.0-S0300908424000701-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338045","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}