Biochimie最新文献_第8页

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-11 DOI: 10.1016/S0300-9084(24)00056-7

引用次数: 0

Exploring ligand interactions with human phosphomannomutases using recombinant bacterial thermal shift assay and biochemical validation 利用重组细菌热转移分析和生化验证探索配体与人类磷酸甘露聚糖酶的相互作用

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-06 DOI: 10.1016/j.biochi.2024.02.011

Maria Monticelli , Bruno Hay Mele , Demi Marie Wright , Simone Guerriero , Giuseppina Andreotti , Maria Vittoria Cubellis

引用次数: 0

Enhancement of intrinsic guanine fluorescence by protonation in DNA of various structures 不同结构 DNA 中质子化作用对鸟嘌呤本征荧光的增强。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-04 DOI: 10.1016/j.biochi.2024.03.003

Liana L. Tevonyan , Natalia P. Bazhulina , Dmitry N. Kaluzhny

{"title":"Enhancement of intrinsic guanine fluorescence by protonation in DNA of various structures","authors":"Liana L. Tevonyan , Natalia P. Bazhulina , Dmitry N. Kaluzhny","doi":"10.1016/j.biochi.2024.03.003","DOIUrl":"10.1016/j.biochi.2024.03.003","url":null,"abstract":"<div><p>Understanding the diversity of DNA structure and functions in biology requires tools to study this biomolecule selectively and thoroughly. Fluorescence methods are powerful technique for non-invasive research. Due to the low quantum yield, the intrinsic fluorescence of nucleotides has not been considered for use in the detection and differentiation of nucleic acid bases. Here, we have studied the influence of protonation of nucleotides on their fluorescence properties. We show that protonation of ATP and GTP leads to enhanced intrinsic fluorescence. Fluorescence enhancement at acidic pH has been observed for double-stranded DNA and single-stranded oligonucleotides. The formation of G4 secondary structures apparently protected certain nucleotides from protonation, resulting in less pronounced fluorescence enhancement. Furthermore, acid-induced depurination under protonation was less noticeable in G4 structures than in double-stranded and single-stranded DNA. We show that changes in the intrinsic fluorescence of guanine can be used as a sensitive sensor for changes in the structure of the DNA and for the protonation of specific nucleotides.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051310","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}

引用次数: 0

History of Tspo deletion and induction in vivo: Phenotypic outcomes under physiological and pathological situations 体内 Tspo 缺失和诱导的历史：生理和病理情况下的表型结果。

IF 3.3 3区生物学

Biochimie Pub Date : 2024-03-02 DOI: 10.1016/j.biochi.2024.03.001

{"title":"History of Tspo deletion and induction in vivo: Phenotypic outcomes under physiological and pathological situations","authors":"","doi":"10.1016/j.biochi.2024.03.001","DOIUrl":"10.1016/j.biochi.2024.03.001","url":null,"abstract":"<div><p>The mitochondrial translocator protein (TSPO) is an outer mitochondrial protein membrane with high affinity for cholesterol. It is expressed in most tissues but is more particularly enriched in steroidogenic tissues. TSPO is involved in various biological mechanisms and TSPO regulation has been related to several diseases. However, despite a considerable number of published studies interested in TSPO over the past forty years, the precise function of the protein remains obscure. Most of the functions attributed to TSPO have been identified using pharmacological ligands of this protein, leading to much debate about the accuracy of these findings. In addition, research on the physiological role of TSPO has been hampered by the lack of <em>in vivo</em> deletion models. Studies to perform genetic deletion of <em>Tspo</em> in animal models have long been unsuccessful, which led to the conclusions that the deletion was deleterious and the gene essential to life. During the last decades, thanks to the significant technical advances allowing genome modification, several models of animal genetically modified for TSPO have been developed. These models have modified our view regarding TSPO and profoundly improved our fundamental knowledge on this protein. However, to date, they did not allow to elucidate the precise molecular function of TSPO and numerous questions persist concerning the physiological role of TSPO and its future as a therapeutic target. This article chronologically reviews the development of deletion and induction models of TSPO.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000518/pdfft?md5=69a5d8ea662224d2c271bfe0feb1fdc7&pid=1-s2.0-S0300908424000518-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023684","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}

引用次数: 0

Biochemical and metabolic characterization of a G6PC2 inhibitor 一种 G6PC2 抑制剂的生化和代谢特征。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-01 DOI: 10.1016/j.biochi.2024.02.012

Emily M. Hawes , Mohsin Rahim , Zeinab Haratipour , Abigail R. Orun , Margaret L. O'Rourke , James K. Oeser , Kwangho Kim , Derek P. Claxton , Ray D. Blind , Jamey D. Young , Richard M. O'Brien

{"title":"Biochemical and metabolic characterization of a G6PC2 inhibitor","authors":"Emily M. Hawes , Mohsin Rahim , Zeinab Haratipour , Abigail R. Orun , Margaret L. O'Rourke , James K. Oeser , Kwangho Kim , Derek P. Claxton , Ray D. Blind , Jamey D. Young , Richard M. O'Brien","doi":"10.1016/j.biochi.2024.02.012","DOIUrl":"10.1016/j.biochi.2024.02.012","url":null,"abstract":"<div><p>Three glucose-6-phosphatase catalytic subunits, that hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate, have been identified, designated G6PC1-3, but only G6PC1 and G6PC2 have been implicated in the regulation of fasting blood glucose (FBG). Elevated FBG has been associated with multiple adverse clinical outcomes, including increased risk for type 2 diabetes and various cancers. Therefore, G6PC1 and G6PC2 inhibitors that lower FBG may be of prophylactic value for the prevention of multiple conditions. The studies described here characterize a G6PC2 inhibitor, designated VU0945627, previously identified as Compound 3. We show that VU0945627 preferentially inhibits human G6PC2 versus human G6PC1 but activates human G6PC3. VU0945627 is a mixed G6PC2 inhibitor, increasing the Km but reducing the Vmax for G6P hydrolysis. PyRx virtual docking to an AlphaFold2-derived G6PC2 structural model suggests VU0945627 binds two sites in human G6PC2. Mutation of residues in these sites reduces the inhibitory effect of VU0945627. VU0945627 does not inhibit mouse G6PC2 despite its 84% sequence identity with human G6PC2. Mutagenesis studies suggest this lack of inhibition of mouse G6PC2 is due, in part, to a change in residue 318 from histidine in human G6PC2 to proline in mouse G6PC2. Surprisingly, VU0945627 still inhibited glucose cycling in the mouse islet-derived βTC-3 cell line. Studies using intact mouse liver microsomes and PyRx docking suggest that this observation can be explained by an ability of VU0945627 to also inhibit the G6P transporter SLC37A4. These data will inform future computational modeling studies designed to identify G6PC isoform-specific inhibitors.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000506/pdfft?md5=f0b9f5d8865252946de4d7a5cd3b9247&pid=1-s2.0-S0300908424000506-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023682","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}

引用次数: 0

Elucidating the pivotal role of TSPO in porphyrin-related cellular processes, in Bacillus cereus 阐明 TSPO 在蜡样芽孢杆菌卟啉相关细胞过程中的关键作用。

IF 3.3 3区生物学

Biochimie Pub Date : 2024-02-27 DOI: 10.1016/j.biochi.2024.02.008

{"title":"Elucidating the pivotal role of TSPO in porphyrin-related cellular processes, in Bacillus cereus","authors":"","doi":"10.1016/j.biochi.2024.02.008","DOIUrl":"10.1016/j.biochi.2024.02.008","url":null,"abstract":"<div><p>A structural homolog of the mammalian TSPO has been identified in the human pathogen <em>Bacillus cereus</em>. BcTSPO, in its recombinant form, has previously been shown to bind and degrade porphyrins. In this study, we generated a Δ<em>tspO</em> mutant strain in <em>B. cereus</em> ATCC 14579 and assessed the impact of the absence of BcTSPO on cellular proteomics and physiological characteristics. The proteomic analysis revealed correlations between the lack of BcTSPO and the observed growth defects, increased oxygen consumption, ATP deficiency, heightened tryptophan catabolism, reduced motility, and impaired biofilm formation in the Δ<em>tspO</em> mutant strain. Our results also suggested that BcTSPO plays a crucial role in regulating intracellular levels of metabolites from the coproporphyrin-dependent branch of the heme biosynthetic pathway. This regulation potentially underlies alterations in the metabolic landscape, emphasizing the pivotal role of BcTSPO in <em>B. cereus</em> aerobic metabolism. Notably, our study unveils, for the first time, the involvement of TSPO in tryptophan metabolism. These findings underscore the multifaceted role of TSPO, not only in metabolic pathways but also potentially in the microorganism's virulence mechanisms.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000464/pdfft?md5=8ff2076f74a176943f8e38c3f791bd1d&pid=1-s2.0-S0300908424000464-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998579","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}

引用次数: 0

Benefits of rutin on mitochondrial function and inflammation in an aluminum-induced neurotoxicity rat model: Potential interest for the prevention of neurodegeneration 芦丁对铝诱导神经毒性大鼠模型线粒体功能和炎症的益处：预防神经变性的潜在意义

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-24 DOI: 10.1016/j.biochi.2024.02.010

Khadidja Kessas , Wafaa Lounis , Zehor Chouari , Anne Vejux , Gérard Lizard , Omar Kharoubi

{"title":"Benefits of rutin on mitochondrial function and inflammation in an aluminum-induced neurotoxicity rat model: Potential interest for the prevention of neurodegeneration","authors":"Khadidja Kessas , Wafaa Lounis , Zehor Chouari , Anne Vejux , Gérard Lizard , Omar Kharoubi","doi":"10.1016/j.biochi.2024.02.010","DOIUrl":"10.1016/j.biochi.2024.02.010","url":null,"abstract":"<div><p>Rutin, a phenolic compound, exhibits a diverse range of biological properties, including antioxidant, anti-inflammatory, and antimicrobial effects. In this study, we aimed to investigate the potential of rutin, a naturally occurring plant bioactive molecule, to mitigate the neurotoxic effects induced by aluminum chloride (AlCl<sub>3</sub>). Over a period of 6 weeks, rats were intraperitoneally injected with AlCl<sub>3</sub> at a weekly dose of 60 mg/kg, while rutin treatment was administered orally via gavage at a daily dose of 30 mg/kg. AlCl<sub>3</sub> exposure resulted in a significant increase lipid peroxidation (LPO) by 316.24%, nitrate levels by 504.14%, and tumor necrosis factor-alpha (TNF-α) levels by 93.82% in brain mitochondria. Additionally, AlCl<sub>3</sub> exposure led to a reduction in glutathione levels and the activity of antioxidant enzymes, including superoxide dismutase (SOD) by 19.74%, glutathione peroxidase (GPx) by 44.76%, and catalase by 50.50%. There was also a significant decline in the activity of mitochondrial complex enzymes. In contrast, rutin treatment significantly enhanced the activity of antioxidant enzymes while concurrently reducing lipid peroxidation levels in rats. Specifically, rutin administration exerted a modulatory effect on the inflammatory response triggered by aluminum exposure, effectively suppressing the excessive production of nitrate and TNF-α. These findings highlight the potential of rutin as an effective therapeutic strategy in mitigating and combating neuro-inflammation and oxidative stress associated with aluminum-induced toxicity, thereby effectively restoring mitochondrial function.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974973","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}

引用次数: 0

Characterization of SLA RNA promoter from dengue virus and its interaction with the viral non-structural NS5 protein 登革热病毒 SLA RNA 启动子的特征及其与病毒非结构 NS5 蛋白的相互作用

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-24 DOI: 10.1016/j.biochi.2024.02.005

Karl Brillet , Marta Janczuk-Richter , Amanda Poon , Joanne Laukart-Bradley , Eric Ennifar , Isabelle Lebars

{"title":"Characterization of SLA RNA promoter from dengue virus and its interaction with the viral non-structural NS5 protein","authors":"Karl Brillet , Marta Janczuk-Richter , Amanda Poon , Joanne Laukart-Bradley , Eric Ennifar , Isabelle Lebars","doi":"10.1016/j.biochi.2024.02.005","DOIUrl":"10.1016/j.biochi.2024.02.005","url":null,"abstract":"<div><p>The Dengue virus (DENV) is the most significant arthropod-borne viral pathogen in humans with 400 million infections annually. DENV comprises four distinct serotypes (DENV-1 to -4) which complicates vaccine development. Any of the four serotypes can cause clinical illness but with distinctive infection dynamics. Variations in sequences identified within the four genomes induce structural differences in crucial RNA motifs that were suggested to be correlated to the degree of pathogenicity among DENV-1 to -4. In particular, the RNA Stem-loop A (SLA) at the 5′-end of the genome, acts as a key regulator of the viral replication cycle by interacting with the viral NS5 polymerase to initiate the minus-strand viral RNA synthesis and later to methylate and cap the synthesized RNA. The molecular details of this interaction remain not fully described. Here, we report the solution secondary structures of SLA from DENV-1 to -4. Our results highlight that the four SLA exhibit structural and dynamic differences. Secondly, to determine whether SLA RNA contains serotype-specific determinants for the recognition by the viral NS5 protein, we investigated interactions between SLA from DENV -1 to -4 and DENV2 NS5 using combined biophysical approaches. Our results show that NS5 from DENV2 is able to bind SLA from other serotypes, but that other viral or host factors may be necessary to stabilize the complex and promote the catalytically active state of the NS5. By contrast, we show that a serotype-specific binding is driven by specific interactions involving conformational changes within the SLA RNA.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139955510","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}

引用次数: 0

The ‘Not-So-Famous Five’ in tumorigenesis: tRNAs, tRNA fragments, and tRNA epitranscriptome in concert with AARSs and AIMPs 肿瘤发生过程中的 "非著名五人组"：tRNAs、tRNA 片段、tRNA 表转录组与 AARSs 和 AIMPs 的协同作用。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-23 DOI: 10.1016/j.biochi.2024.02.004

Sutapa Saha , Biyas Mukherjee , Proma Banerjee , Debadrita Das

{"title":"The ‘Not-So-Famous Five’ in tumorigenesis: tRNAs, tRNA fragments, and tRNA epitranscriptome in concert with AARSs and AIMPs","authors":"Sutapa Saha , Biyas Mukherjee , Proma Banerjee , Debadrita Das","doi":"10.1016/j.biochi.2024.02.004","DOIUrl":"10.1016/j.biochi.2024.02.004","url":null,"abstract":"<div><p>RNA profiling studies have revealed that ∼75% of the human genome is transcribed to RNA but only a meagre fraction of it is translated to proteins. Majority of transcribed RNA constitute a specialized pool of non-coding RNAs. Human genome contains approximately 506 genes encoding a set of 51 different tRNAs, constituting a unique class of non-coding RNAs that not only have essential housekeeping functions as translator molecules during protein synthesis, but have numerous uncharted regulatory functions. Intriguing findings regarding a variety of non-canonical functions of tRNAs, tRNA derived fragments (tRFs), esoteric epitranscriptomic modifications of tRNAs, along with aminoacyl-tRNA synthetases (AARSs) and ARS-interacting multifunctional proteins (AIMPs), envision a ‘peripheral dogma’ controlling the flow of genetic information in the backdrop of qualitative information wrung out of the long-live central dogma of molecular biology, to drive cells towards either proliferation or differentiation programs. Our review will substantiate intriguing peculiarities of tRNA gene clusters, atypical tRNA-transcription from internal promoters catalysed by another distinct RNA polymerase enzyme, dynamically diverse tRNA epitranscriptome, intricate mechanism of tRNA-charging by AARSs governing translation fidelity, epigenetic regulation of gene expression by tRNA fragments, and the role of tRNAs and tRNA derived/associated molecules as quantitative determinants of the functional proteome, covertly orchestrating the process of tumorigenesis, through a deregulated tRNA-ome mediating selective codon-biased translation of cancer related gene transcripts.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944768","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}

引用次数: 0

Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani 吡哆醛激酶基因缺失导致唐氏利什曼病生长受阻、氧化还原代谢紊乱和细胞周期停滞

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-23 DOI: 10.1016/j.biochi.2024.02.009

Pradyot Kumar Roy , Anindita Paul , Sandra Lalchhuanawmi , Neerupudi Kishore Babu , Sushma Singh

{"title":"Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani","authors":"Pradyot Kumar Roy , Anindita Paul , Sandra Lalchhuanawmi , Neerupudi Kishore Babu , Sushma Singh","doi":"10.1016/j.biochi.2024.02.009","DOIUrl":"10.1016/j.biochi.2024.02.009","url":null,"abstract":"<div><p>Pyridoxal kinase (PdxK) is a vitamin B<sub>6</sub> salvage pathway enzyme which produces pyridoxal phosphate. We have investigated the impact of PdxK deletion in <em>Leishmania donovani</em> on parasite survivability, infectivity and cellular metabolism. <em>Ld</em>PdxK mutants were generated by gene replacement strategy. All mutants showed significant reduction in growth in comparison to wild type. For PdxK mediated biochemical perturbations, only heterozygous mutants and complementation mutants were used as the growth of null mutants were compromised. Heterozygous mutant showed reduction <em>in</em> <em>vitro</em> infectivity and higher cytosolic and mitochondrial ROS levels. Glutathione levels decreased significantly in heterozygous mutant indicating its involvement in cellular oxidative metabolism. Pyridoxal kinase gene deletion resulted in reduced ATP levels in parasites and arrest at G<sub>0</sub>/G<sub>1</sub> phase of cell cycle. All these perturbations were rescued by PdxK gene complementation. This is the first report to confirm that <em>Ld</em>PdxK plays an indispensable role in cell survival, pathogenicity, redox metabolism and cell cycle progression of <em>L. donovani</em> parasites. These results provide substantial evidence supporting PdxK as a therapeutic target for the development of specific antileishmanial drug candidates.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139955558","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}

引用次数: 0