International Journal of Biochemistry & Cell Biology最新文献

{"title":"Cannabigerol – A potent regulator of insulin sensitivity in rat’s skeletal muscle via targeting the sphingolipid metabolism and PI3K/Akt/mTOR pathway?","authors":"Patrycja Bielawiec ,&nbsp;Lara Swierkot ,&nbsp;Karolina Konstantynowicz-Nowicka ,&nbsp;Adrian Chabowski ,&nbsp;Agnieszka Błachnio-Zabielska ,&nbsp;Ewa Harasim-Symbor","doi":"10.1016/j.biocel.2025.106819","DOIUrl":"10.1016/j.biocel.2025.106819","url":null,"abstract":"<div><div>Despite the great advances in medicine, there is a compelling need to develop alternative strategies to effectively treat obesity with the use of plant-origin therapeutics. Cannabigerol (CBG) appears to be a novel promising compound for managing this increasingly prevalent disease requiring multifaceted pharmacotherapy. Therefore, the herein study aimed to evaluate the potential therapeutic properties of 2-week CBG administration on the muscular metabolism of sphingolipids as well as insulin signal transduction pathway in a rat model of obesity and insulin resistance (IR) induced by high-fat, high-sucrose (HFHS) diet. The high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) were used to determine the sphingolipids content, while the multiplex assay kit was applied to measure the level of the phosphorylated form of proteins from the PI3K/Akt/mTOR pathway. The expression of various proteins engaged in the sphingolipid metabolism and insulin signaling was assessed using Western blotting. Our results showed that 2-week CBG treatment decreased the muscular content of most deleterious C16:0-Cer and C18:0-Cer ceramide species and reduced the intramuscular concentrations of sphinganine (SFA) and sphingosine (SFO), redirecting their metabolism toward phosphorylated derivatives, sphinganine-1-phosphate (SFA1P), and sphingosine-1-phosphate (S1P), respectively. Simultaneously, CBG counteracted S1P efflux in skeletal muscle, inhibiting the tissue-specific S1P/S1PR3 signaling. CBG also activated the PI3K/Akt/mTOR pathway, which increased the phosphorylation of protein kinase B (Akt) and its downstream targets in the myocytes of obese rats. These results suggest that CBG may play an essential homeostatic role in skeletal muscles and can protect from the development of obesity-associated metabolic derangements.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106819"},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242819","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":"Bifidobacterium apoptosis induction by measuring bax and caspases on SW948 human colon cancer cell line","authors":"Maryam Soraya ,&nbsp;Elham Moazamian ,&nbsp;Seyedeh Azra Shamsdin ,&nbsp;Mehdi Dehghani","doi":"10.1016/j.biocel.2025.106813","DOIUrl":"10.1016/j.biocel.2025.106813","url":null,"abstract":"<div><h3>Background</h3><div>Nowadays, probiotic bacteria have been considered as a factor in the prevention and treatment of cancer, especially by induction of apoptosis. The aim of study, the isolation and identification of <em>Bifidobacterium</em> SPP, and to investigate the effects of bacterial cell extract and cell free supernatants (CFS) was on normal cell line and colon cancer cell line through measuring caspases.</div></div><div><h3>Material and method</h3><div>In this study, dairy products were collected and After isolation and identification of <em>Bifidobacterium</em> via PCR method, the cytotoxicity effects of cell free supernatants (CFS) (<em>B.Bifidum</em> S2 and <em>B.Bifidum</em> S3) and bacterial cell extract (<em>B.Bifidum</em> P6 and <em>B.Bifidum</em> P17) on colon cancer cell line (SW948) and normal cell line (HEK-293) were evaluated using MTT assay. The effect of isolated bacterial strains on apoptotic cells was determined by measuring caspases 1, 3, 9 and Bax by using ELISA kit.</div></div><div><h3>Result</h3><div>The results showed that the cytotoxicity effect of CFS was higher than bacterial cell extract. CFS showed the highest cytotoxicity effect (about 95 %) on colon cancer cell line. Quantitative analysis of Caspase-1, −3, 9, and Bax expression demonstrated that CFS may exert anticancer effects through induced apoptosis.</div></div><div><h3>Conclusion</h3><div>The results of the present research indicate that probably <em>B.Bifidum</em> S2 and <em>B.Bifidum</em> S3 isolates may be prevent colon cancer by inducing apoptosis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106813"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235797","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":"Medium-dose irradiation impairs long-term hematopoietic stem cell functionality and hematopoietic resilience to cytotoxic stress","authors":"Qinyu Zhang ,&nbsp;Anna Rydström ,&nbsp;Isabel Hidalgo ,&nbsp;Jörg Cammenga ,&nbsp;Alexandra Rundberg Nilsson","doi":"10.1016/j.biocel.2025.106814","DOIUrl":"10.1016/j.biocel.2025.106814","url":null,"abstract":"<div><div>Irradiation and 5-fluorouracil (5-FU) are widely utilized tools in hematopoietic research to generate myeloablation and assess blood recovery dynamics. A comprehensive understanding of their effects on the hematopoietic system is essential for optimizing therapeutic strategies, refining experimental models to modulate hematotoxicity, and interpreting research outcomes. Despite their widespread application, the long-term hematopoietic impacts of irradiation and 5-FU, particularly on hematopoietic stem cells (HSCs), remain incompletely characterized. In this study, we therefore examined the long-term effects of 2 Gy medium-dose ionizing radiation (MDIR) and 150 mg/kg 5-FU on HSCs and the hematopoietic system’s resilience to subsequent cytotoxic stress in mice. Our findings demonstrate that MDIR, but not 5-FU, induces sustained impairments in HSC function and results in the selective depletion of MHC class II^- HSCs – a subset characterized by high self-renewal potential and hypersensitivity to irradiation-induced ROS production. Furthermore, MDIR significantly compromised hematopoietic recovery following a subsequent 5-FU challenge, as evidenced by substantially reduced platelet and red blood cell (RBC) counts during the critical recovery phase. These findings highlight the distinct and persistent impacts of MDIR and 5-FU on HSCs and hematopoietic function, revealing crucial differences in their mechanisms of action and long-term consequences on the hematopoietic system.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106814"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221207","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":"p38 MAPK–mediated upregulation of claudin-3 and claudin-4 by gemcitabine contributes to chemoresistance in ovarian cancer","authors":"Jiaxin Zhao ,&nbsp;Jianli Ke ,&nbsp;Xiaochao Cao ,&nbsp;Jie Li ,&nbsp;Mingzhen Gu ,&nbsp;Xiaoling Zhou ,&nbsp;Yinglu Yan ,&nbsp;Jiyuan Ke","doi":"10.1016/j.biocel.2025.106805","DOIUrl":"10.1016/j.biocel.2025.106805","url":null,"abstract":"<div><div>Chemotherapy is a primary therapeutic option in cancer treatment, but often associated with unwanted side effects and drug resistance. Claudin-3 (CLDN3) and claudin-4 (CLDN4) are essential components of tight junctions, frequently overexpressed in ovarian cancer, serve as potential therapeutic targets. In this study, we utilized flow cytometry, qPCR, Western blot, and animal experiments to investigate the regulation of CLDN3 and CLDN4 by chemotherapy drug, gemcitabine, in the ovarian cancer cell line A2780. We reported that gemcitabine can induce expression of CLDN3 and CLDN4 in ovarian cancer cells. Mechanistically, we showed that gemcitabine induces expression of CLDN3 and CLDN4 through p38 MAP kinase mediated transcriptional regulation. Overexpression of CLDN3 or CLDN4 functionally protected A2780 ovarian cancer from gemcitabine induced cell killing. It appears that gemcitabine induced expression of CLDN3/4 is a chemoresistance mechanism for cancer cells. Gemcitabine-induced upregulation of CLDN3/4 suggests that ovarian cancer cells may be more effectively targeted using claudin-3/4-specific antibodies or antibody-drug conjugates (ADCs) in combination with chemotherapy, which could have clinical implications for ovarian cancer treatment in the future.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106805"},"PeriodicalIF":3.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116978","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":"Serine phosphorylation of protein arginine methyltransferase Hmt1 is critical for controlling its protein levels","authors":"Sai Wu ,&nbsp;Vincent Rossi ,&nbsp;Christopher A. Jackson ,&nbsp;Isabella Lonardo ,&nbsp;Joseph A. Ricottone ,&nbsp;Joan M. Hevel ,&nbsp;Michael C. Yu","doi":"10.1016/j.biocel.2025.106790","DOIUrl":"10.1016/j.biocel.2025.106790","url":null,"abstract":"<div><div>In eukaryotes, protein arginine methylation is a prevalent post-translational modification found in a multitude of proteins responsible for key biological processes, ranging from transcription to signaling. One model suggests that phosphorylation of serine 9 (S9) in the <em>Saccharomyces cerevisiae</em> major protein arginine methyltransferase Hmt1 is critical for its oligomerization and activity. In this study, we used classic biochemical approaches to demonstrate that neither the S9 phosphomimetic nor the non-phosphorylatable substitution mutants of Hmt1 affect its oligomerization. These mutants remain active <em>in vivo,</em> retaining their ability to methylate the SR-/hnRNP-like protein Npl3 and displaying a monomethylarginine and asymmetric dimethylarginine banding profile similar to that of the wild-type. In cells lacking Dbf2, the proposed kinase responsible for phosphorylating Hmt1 at S9, Npl3 remains methylated. Additionally, monomethylarginine and asymmetric dimethylarginine banding profiles in cells lacking Dbf2 mostly resemble those observed in the wild-type rather than in <em>hmt1Δ</em> cells. Synchronized yeast cells expressing either S9 substitution exhibit entry into the M phase of the cell cycle at a rate similar to that of both wild-type and <em>hmt1Δ</em> cells. Our results suggest that the C-terminal epitope tagging of Hmt1 is responsible for the previously observed loss of enzymatic activities, rather than the S9 phosphorylation status of Hmt1. Finally, we demonstrate that S9 phosphorylation plays a role in maintaining Hmt1 protein levels <em>in vivo</em>. Overall, our finding demonstrates a novel role for Hmt1 S9 phosphorylation in tuning its <em>in vivo</em> protein levels.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106790"},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121277","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":"Clostridium butyricum protects the ileal barrier in mice by regulating the farnesoid X receptor signaling pathway","authors":"Hanfei Wang ,&nbsp;Li Hou ,&nbsp;Xintong Chen ,&nbsp;Linling Gui ,&nbsp;Weiwei Jiang ,&nbsp;Weibing Tang","doi":"10.1016/j.biocel.2025.106798","DOIUrl":"10.1016/j.biocel.2025.106798","url":null,"abstract":"<div><h3>Background</h3><div>The intestinal barrier has an important role in maintaining homeostasis. The aim of this study was to determine the protective effect of <em>Clostridium butyricum</em> (CBM) on small intestinal barrier damage in mice and the role of farnesoid X receptor (FXR) in regulating the intestinal barrier by <em>C. butyricum</em>.</div></div><div><h3>Methods and results</h3><div>A model of small intestinal injury induced by dextran sulfate sodium (DSS) was constructed to detect repair of intestinal barrier damage after feeding with <em>C. butyricum</em>. In the DSS model group, expression of the tight junction protein (TJP) was significantly decreased and expression of inflammatory factors was significantly increased. TJP expression was significantly increased and inflammatory factor expression was significantly decreased after <em>C. butyricum</em> feeding, which indicated that intestinal barrier function was repaired. In addition, inhibition of FXR expression as well as the downstream signaling pathways were demonstrated in the DSS model group. FXR and its downstream signaling pathways were significantly upregulated after feeding with <em>C. butyricum</em>. Then, intestinal barrier function was evaluated by constructing an intestinal-specific FXR knockout (KO) DSS model in mice. Suppression of TJP and upregulated expression of inflammatory factors were detected in the KO DSS group but there was no significant difference in the expression of TJP and inflammatory factors after <em>C. butyricum</em> feeding. Furthermore, there was no significant difference in FXR downstream signaling pathway expression after <em>C. butyricum</em> feeding compared to the KO DSS group. <em>C. butyricum</em> supernatants (CSs) upregulated the FXR signaling pathways <em>in vitro</em>. CSs did not activate the FXR signaling pathway when FXR was suppressed.</div></div><div><h3>Conclusions</h3><div><em>C. butyricum</em> supplementation effectively ameliorated DSS-induced intestinal barrier disruption. <em>C. butyricum</em> may have a protective effect on the small intestine through the FXR signaling pathway.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106798"},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121274","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":"ARHGAP11A is a potential prognostic biomarker and therapeutic target for pancreatic adenocarcinoma","authors":"Qiu-ai Shu ,&nbsp;Xin-di Huang ,&nbsp;Jian Wu ,&nbsp;Xi-ru Liang ,&nbsp;Ya-lan Wang ,&nbsp;Jin-min Yu ,&nbsp;Zi-wei Wang ,&nbsp;Na Liu ,&nbsp;Jin-hai Wang ,&nbsp;Ning Xie","doi":"10.1016/j.biocel.2025.106804","DOIUrl":"10.1016/j.biocel.2025.106804","url":null,"abstract":"<div><div>The prognosis of pancreatic adenocarcinoma remains dismal up to now, partly owing to a lack of clinically feasible therapeutic targets. ARHGAP11A, a member of Rho GTPase-activating proteins family, has been reported as a prognostic biomarker and oncogene for multiple cancers. However, the specific effects of ARHGAP11A in pancreatic adenocarcinoma remain obscure. In this study, we explored and validated the oncogenic role of ARHGAP11A in pancreatic adenocarcinoma via thorough bioinformatics analyses of public databases and our own RNA-seq data, and <em>in vitro</em> experiments. We found that ARHGAP11A was significantly upregulated in pancreatic adenocarcinoma and correlated with poor clinical outcomes of pancreatic adenocarcinoma patients. Functional enrichment analyses revealed that ARHGAP11A-related genes were enriched in pathways of cell cycle and cell apoptosis. Further molecular functional experiments on ARHGAP11A knockdown pancreatic adenocarcinoma cell lines demonstrated that ARHGAP11A knockdown significantly inhibited cell proliferation, promoted cell cycle arrest in the G1/S stage, and induced cell apoptosis. In comparison, overexpression of ARHGAP11A could remarkably promote the proliferation, cell cycle progression, and apoptosis resistance of pancreatic adenocarcinoma cells. In conclusion, our study demonstrates that ARHGAP11A plays an oncogenic role in pancreatic adenocarcinoma, thus providing a novel therapeutic target and prognostic biomarker for patients with pancreatic adenocarcinoma.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106804"},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107719","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 role of argininosuccinate lyase in TAp73-mediated proliferating tumor cells","authors":"Jie Zhang ,&nbsp;Min Zhao ,&nbsp;Haolan Zhang,&nbsp;Chenjie Ma,&nbsp;Chunyan Ma,&nbsp;Le Li","doi":"10.1016/j.biocel.2025.106803","DOIUrl":"10.1016/j.biocel.2025.106803","url":null,"abstract":"<div><div>The dysregulation of the urea cycle resulting in an excessive buildup of ammonia is identified as a pivotal mechanism driving tumor progression. In particular, argininosuccinate lyase (ASL) is crucial for cancer cell proliferation, cleaves argininosuccinic acid to produce arginine and fumarate in the urea cycle. However, the mechanisms controlling ASL expression in cancer cells remain unclear. Herein, we found that TAp73, a transcription factor within the p53 family, regulates the urea cycle pathway in tumor cells with mutant or null p53. Deletion of TAp73 led to increased accumulation of ammonia and changes in urea cycle metabolites. Subsequent experimentation involving the suppression of TAp73 substantiated its pronounced capability in impeding tumor proliferation and tumorigenicity in both in vitro and in vivo settings. Chromatin immunoprecipitation revealed that TAp73 could bind to specific sequences in the <em>ASL</em> promoter, thus promoting ASL expression, increasing intracellular arginine, and reducing ammonia levels. This investigation undertook a clinical scrutiny of TAp73 expression levels in tumor patients' transcriptomes, revealing an inverse relationship between TAp73 expression and patient survival. These results suggested that TAp73 led to abnormalities in the urea cycle by enhancing ASL expression and will be an important factor in promoting tumor proliferation and a potential target for tumor drugs.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106803"},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095529","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":"Deciphering the molecular heterogeneity of soft tissue sarcoma by integrating multiomics and single cell sequence","authors":"Haixiang Zhang ,&nbsp;Peng Luo ,&nbsp;Hao Jiang ,&nbsp;Aimin Jiang ,&nbsp;Wei Wei ,&nbsp;Chunbiao Wu","doi":"10.1016/j.biocel.2025.106801","DOIUrl":"10.1016/j.biocel.2025.106801","url":null,"abstract":"<div><h3>Background</h3><div>Soft tissue sarcoma is a highly malignant tumor with extensive heterogeneity across multiple omics. However, a comprehensive multi-omics subtyping system has not yet been established.</div></div><div><h3>Methods</h3><div>We integrated sarcoma multi-omics data, including clinical information, transcriptome expression profiles, DNA methylation, and somatic mutations. Using ten advanced clustering algorithms, we identified robust subtypes and validated the reproducibility of our analysis in two independent external datasets. We also identified subtype-specific treatment strategies and analyzed the differences in microenvironments between subtypes using single-cell data.</div></div><div><h3>Results</h3><div>Based on multi-omics subtyping, we identified two novel sarcoma molecular subtypes, named sarcoma multi-omics subtype 1 (SAMS1) and SAMS2. SAMS2 exhibited a poorer prognosis, with significantly activated Myc, glycolysis, and Wnt beta-catenin signaling pathways. SAMS2 was characterized by a lower abundance of immune cell infiltration and anti-tumor immunity deficiency, which owned a lower response rate to immunotherapy but was sensitive to certain targeted drugs, including pazopanib, axitinib, thapsigargin, and elesclomol. MK886 and NU1025 were identified as effective therapeutic targets for the SAMS2. In SAMS2-like tumor epithelial cells, <em>HOXB13</em>/<em>COL16A1</em> and <em>BASP1</em> regulated epithelial-mesenchymal transition. We found that <em>WNT7B</em> was highly expressed in STS and was associated with poor patient prognosis, suggesting its potential as a novel therapeutic target for STS patients.</div></div><div><h3>Conclusion</h3><div>The STS molecular subtyping system based on multi-omics data effectively distinguishes patients with poor prognosis. The subtyping results are robust and reliable, providing new insights for the precise diagnosis and treatment of these patients.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106801"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089881","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":"Mycobacterium tuberculosis curli pili reduces oxygen consumption rate of THP-1 macrophages during early infection","authors":"Shinese Ashokcoomar ,&nbsp;Tarien J. Naidoo ,&nbsp;Bridgette M. Cumming ,&nbsp;Zainab Baig ,&nbsp;Barry Truebody ,&nbsp;Jared S. Mackenzie ,&nbsp;Adrie J.C. Steyn ,&nbsp;Manormoney Pillay","doi":"10.1016/j.biocel.2025.106802","DOIUrl":"10.1016/j.biocel.2025.106802","url":null,"abstract":"<div><div>The development of improved anti-tuberculosis (TB) strategies to address drug-resistance and ineffectual TB treatment regimens should focus on interrupting the initial host-pathogen interaction. This study aimed to elucidate the effect of surface-located adhesin, <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) curli pili (MTP), on the bioenergetic and metabolomic profiles of THP-1 macrophages during initial stages of infection. Differentiated THP-1 macrophages were infected with wildtype (WT), ∆<em>mtp</em>, or <em>mtp</em>-complemented strains of <em>Mtb</em>. Bioenergetic profiles and metabolic flux were determined and statistical analysis highlighted differences/similarities amongst the THP-1 macrophage groups. The ∆<em>mtp</em> infected THP-1 macrophages mimicked the higher oxygen consumption rate (OCR) for basal respiration, ATP production, maximal respiration and spare respiratory capacity of the uninfected THP-1 macrophages, relative to the WT and <em>mtp</em>-complement infected THP-1 macrophages. The ∆<em>mtp</em> infected THP-1 macrophages displayed the highest compensatory glycolytic rate. <em>Mtb</em> infection caused the redirection of carbon from the tricarboxylic acid cycle to glycolysis, in addition to an increased flux through the pentose phosphate pathway. However, in the ∆<em>mtp</em> infected THP-1 macrophages, the total metabolite abundance was lower, similar to the uninfected THP-1 macrophages. Data indicates that the absence of MTP facilitates prompt clearance of the intracellular pathogen before it establishes a successful infection. This implies that the presence of MTP facilitates the survival of the pathogen during the early stages until infection is established. These findings support the growing evidence that the MTP adhesin is an important virulence factor and interruption of the interaction between pathogen and host, will facilitate swift clearance of the infection by the host.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106802"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070670","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}