FEBS Open Bio最新文献_第4页

Recent insights into the molecular mechanism of ubiquinol oxidation by cytochrome bc₁. 细胞色素bc1氧化泛醇的分子机制研究进展。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-15 DOI: 10.1002/2211-5463.70340

Anna Wójcik-Augustyn, Artur Osyczka, Marcin Sarewicz

{"title":"Recent insights into the molecular mechanism of ubiquinol oxidation by cytochrome bc1.","authors":"Anna Wójcik-Augustyn, Artur Osyczka, Marcin Sarewicz","doi":"10.1002/2211-5463.70340","DOIUrl":"10.1002/2211-5463.70340","url":null,"abstract":"This review summarizes the long-standing effort to understand the mechanism of quinol oxidation catalyzed by cytochrome bc1. Cytochrome bc1 is an enzyme involved in both the respiratory and photosynthetic electron transport chains. It couples quinol oxidation with quinone reduction at two separate active sites (Qo and Qi, respectively) catalyzing proton and electron transfer with high efficiency. At the Qo site, the reaction involves the separation of two electrons derived from the quinol oxidation, which are transferred to opposite sides of the enzyme across the membrane, the so-called electron bifurcation (EB). Despite many years of studies, the molecular mechanism of EB and the molecular basis of its efficiency remain a matter of debate. Here, we reflect on major issues that remain unsolved and thus hamper understanding of EB. We then discuss new perspectives afforded by recent experimental and computational studies that lead to consideration of a new mechanism of EB. This mechanism, named EMergent Electron Transfer (EMET), proposes a departure from a canonical reaction scheme to explain the high fidelity of EB. Ultimately, the theory of EMET provides a constructive conceptual framework for further experimental explorations.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Identification and characterization of a gene conferring stress resistance in Escherichia coli and cyanobacteria. 一种在大肠杆菌和蓝藻中赋予抗逆性的基因的鉴定和表征。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-15 DOI: 10.1002/2211-5463.70343

Akiyo Yamada, Takaaki Tanaka, Manaka Uehara, Keigo Nakano, Ken Morishima, Rintaro Inoue, Masaaki Sugiyama, Masafumi Yohda

{"title":"Identification and characterization of a gene conferring stress resistance in Escherichia coli and cyanobacteria.","authors":"Akiyo Yamada, Takaaki Tanaka, Manaka Uehara, Keigo Nakano, Ken Morishima, Rintaro Inoue, Masaaki Sugiyama, Masafumi Yohda","doi":"10.1002/2211-5463.70343","DOIUrl":"10.1002/2211-5463.70343","url":null,"abstract":"Picosynechococcus sp. strain NKBG15041c is a cyanobacterium isolated from the ocean and while it is known for rapid growth, the basis of its high proliferation capacity remains unclear. Screening for genes which may underlie this rapid growth using E. coli, we identified a gene that promotes growth and enhances stress resistance. The protein encoded by this gene (PcSyn14890) is specific to cyanobacteria, and no homologs with known functions have been identified. In P. NKBG15041c, expression of this gene was induced during the early stage of growth and when introduced into a different cyanobacterium, the transformants exhibited accelerated growth, enhanced stress resistance, and increased ATP and Chlorophyll a content. We hypothesized that PcSyn14890 functions as an ATP-independent chaperone. To investigate further, recombinant PcSyn14890 was expressed in E. coli, purified, and subjected to structural and functional characterization. PcSyn14890 existed as monomers or dimers and did not form higher-order oligomers. Its small-angle X-ray scattering profile was consistent with the AlphaFold3 predicted structure, and the CD spectrum confirmed its β-sheet-rich composition. However, contrary to expectations, PcSyn14890 was unable to prevent the thermal aggregation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Thus, we conclude that PcSyn14890 does not function as a general molecular chaperone and therefore the mechanism by which expression of PcSyn14890 enhances the stress tolerance of E. coli and S. PCC6803 requires further investigation.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Type I interferons modulate autophagy to shape gemcitabine response in pancreatic cancer cells. I型干扰素调节胰腺癌细胞的自噬形成吉西他滨反应。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-15 DOI: 10.1002/2211-5463.70342

Lucy E Bonilla, Martín M Ledesma, Santiago A Behr, Matías A Pibuel, María L Palanek, Daniel H Grasso, Maria N Garcia, Juan Garona, Silvina L Lompardía, Elida Álvarez, Daniela L Papademetrio

{"title":"Type I interferons modulate autophagy to shape gemcitabine response in pancreatic cancer cells.","authors":"Lucy E Bonilla, Martín M Ledesma, Santiago A Behr, Matías A Pibuel, María L Palanek, Daniel H Grasso, Maria N Garcia, Juan Garona, Silvina L Lompardía, Elida Álvarez, Daniela L Papademetrio","doi":"10.1002/2211-5463.70342","DOIUrl":"10.1002/2211-5463.70342","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by poor prognosis and limited response to gemcitabine, the standard first-line chemotherapy. One major contributor to chemoresistance is autophagy, a process frequently upregulated in PDAC. In this study, we examined the ability of type I interferons (IFNα2b and IFNβ1a) to modulate autophagy and disturb tumor cell resistance to gemcitabine. PDAC cells were treated with increasing concentrations of IFNα2b or IFNβ1a, and cell proliferation was assessed by [3H]-thymidine incorporation. Apoptosis was evaluated by TUNEL staining following treatments with interferons and/or gemcitabine. STAT1 phosphorylation was analyzed as a marker of downstream type I interferon signaling. Autophagy was analyzed by western blot for LC3B, Beclin-1, Bcl-XL and p62/SQSTM1, and by quantifying autophagic flux using mCherry-EGFP-LC3B-transfected cells in the presence or absence of lysosomal inhibitors. We found that IFNα2b promoted autophagic flux and reduced gemcitabine-induced cell death, indicating a cytoprotective role. In contrast, IFNβ1a reduced autophagosome formation and significantly enhanced cell death, without clear evidence of altering autophagic flux. Both interferons induced STAT1 phosphorylation, confirming engagement of downstream type I interferon signaling. Our findings highlight the contrasting roles of IFNα2b and IFNβ1a in the regulation of autophagy and gemcitabine response and suggest that IFNβ1a, by reducing autophagosome formation, may sensitize PDAC cells to chemotherapy. These findings identify IFNβ1a as a potential chemosensitizing agent in PDAC and provide a rationale for further evaluating combinations of IFNβ1a, gemcitabine, and autophagy-targeting strategies to overcome chemoresistance.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

IGF2 knockout reduces but does not abolish osteosarcoma growth in vitro and in vivo. IGF2敲除减少但不消除骨肉瘤生长体外和体内。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-12 DOI: 10.1002/2211-5463.70341

Shun Yao, Marco Archetti

引用次数: 0

Exploring the influence of lactoferrin on wound healing and related signaling pathways: a systematic review. 探讨乳铁蛋白对伤口愈合及相关信号通路的影响：系统综述。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-09 DOI: 10.1002/2211-5463.70298

Morgana Lüdtke Azevedo, Kátia Cristiane Hall, Matheus Dos Santos Fernandez, Geovanna Peter Corrêa, Rafael Guerra Lund

{"title":"Exploring the influence of lactoferrin on wound healing and related signaling pathways: a systematic review.","authors":"Morgana Lüdtke Azevedo, Kátia Cristiane Hall, Matheus Dos Santos Fernandez, Geovanna Peter Corrêa, Rafael Guerra Lund","doi":"10.1002/2211-5463.70298","DOIUrl":"10.1002/2211-5463.70298","url":null,"abstract":"This systematic review evaluates the therapeutic efficacy and biological mechanisms of Lactoferrin (Lf) in the wound healing process. The objective was to synthesize evidence regarding its multifunctional role in cellular regeneration, gene modulation, and antimicrobial protection. From an initial screening of 1846 records, 11 in vitro studies (2001-2023) met the eligibility criteria. The synthesized data demonstrate that Lf significantly accelerates the migration and proliferation of human keratinocytes and fibroblasts. At the molecular level, Lf upregulates critical regenerative genes, specifically HAS2 (hyaluronan synthesis) and COL1A1 (collagen type I). Furthermore, Lf exhibits potent inhibitory effects against biofilm formation and bacterial growth, with high efficacy reported against Staphylococcus aureus and Escherichia coli. Thus, Lf acts as a pivotal bioactive agent that bridges regenerative stimulus with antimicrobial defense across all healing phases. Its ability to modulate the extracellular matrix and suppress pathogens suggests it to be a candidate for advanced wound care and regenerative therapies. These findings establish a robust biological rationale for transitioning toward clinical-stage bioprospecting.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Pharmacological inhibition of the PERK pathway modulates hepatocellular carcinoma growth and immune signaling 药理抑制PERK通路调节肝细胞癌的生长和免疫信号。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-04-21 DOI: 10.1002/2211-5463.70252

Ada Lerma-Clavero, Maria Kopsida, Nathalie Arendt, Hans Lennernäs, Markus Sjöblom, Femke Heindryckx

{"title":"Pharmacological inhibition of the PERK pathway modulates hepatocellular carcinoma growth and immune signaling","authors":"Ada Lerma-Clavero, Maria Kopsida, Nathalie Arendt, Hans Lennernäs, Markus Sjöblom, Femke Heindryckx","doi":"10.1002/2211-5463.70252","DOIUrl":"10.1002/2211-5463.70252","url":null,"abstract":"The unfolded protein response (UPR) plays an important role in tumor progression and cellular stress adaptation. In hepatocellular carcinoma (HCC), pharmacological inhibition of the protein kinase R-like endoplasmic reticulum kinase (PERK) is a potential therapeutic strategy, yet its effects on tumor growth and the microenvironment remain unclear. We investigated the selective PERK inhibitor AMG PERK 44 in a diethylnitrosamine (DEN)-induced mouse model of advanced HCC. Tumor burden, proliferation, fibrosis, immune-related gene expression, and ER stress signaling were assessed alongside analyses of single-cell RNA-sequencing data from HCC mouse models and liver-specific PERK knockout mice. Our results show that AMG PERK 44 did not alter tumor number nor cause a decrease in tumor area and proliferation. Furthermore, fibrotic burden was unchanged, although fibrosis architecture and stromal gene expression (TGF-β, CTGF, F4/80) were modified. Despite PERK inhibition, the expression of ER stress associated genes (CHOP, EIF2AK3, ERdj4) increased. Single-cell analysis revealed context-dependent PERK activity, highest in dendritic cells and macrophages under inflammatory and tumor conditions, while PERK knockout livers showed impaired UPR responses after tunicamycin treatment. Finally, AMG PERK 44 did not enhance idarubicin efficacy and caused no major off-target effects. These findings highlight the context-dependent role of PERK in the HCC microenvironment and its implications for targeting UPR pathways in liver cancer.\u0000 ","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1766-1785"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Evaluating GenAI-produced feedback on undergraduate bioscience essays against good higher education feedback practice. 评估genai对本科生物科学论文的反馈与良好的高等教育反馈实践。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 DOI: 10.1002/2211-5463.70339

Annabel Court, Nigel Francis, Andrew Shore, Stephen Rutherford

{"title":"Evaluating GenAI-produced feedback on undergraduate bioscience essays against good higher education feedback practice.","authors":"Annabel Court, Nigel Francis, Andrew Shore, Stephen Rutherford","doi":"10.1002/2211-5463.70339","DOIUrl":"10.1002/2211-5463.70339","url":null,"abstract":"The emergence of generative artificial intelligence (GenAI) has led to substantial interest in its potential to support student learning and assessment in higher education. In particular, GenAI's ability to provide immediate and iterative formative feedback on the quality of students' work has substantial potential to enhance student learning and attainment. However, for feedback to be impactful and useful, the quality and utility of feedback generated by GenAI needs to accurately reflect the quality of the work and align with principles for good feedback provision. This study evaluated the feedback that an undergraduate student might obtain from a single, unscaffolded interaction with a GenAI platform (ChatGPT4o), without tutor input, applied to 30 Year 1 Bioscience essays. Using a bespoke rubric for feedback quality alongside qualitative and quantitative analyses, the GenAI-generated feedback was evaluated for alignment to established hallmarks of good feedback practice. Overall, GenAI-authored feedback had useful elements but was limited in scope. While feedback tended to be accurate, specific to the essay, with a strong focus on content and substantial elements of feed-forward advice, critical guidance and motivational feedback were limited. Within the feedback test, neutral observations focused mostly on structure and use of figures. Positive feedback focused mainly on use of language, and areas for improvement mostly on structure, missing content, and citations/references. These findings suggest that GenAI may have some potential to provide instant, formative guidance to students, but its use may require substantial scaffolding by educators in order to be effective.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

MARK4 enhances stress granule formation under oxidative stress and increases tau accumulation. MARK4促进氧化应激下应激颗粒的形成，增加tau蛋白的积累。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 DOI: 10.1002/2211-5463.70338

Sho Nakajima, Kotone Watanabe, Grigorii Sultanakhmetov, Aoi Fukuchi, Keiya Ito, Sawako Shimizu, Taro Saito, Akiko Asada, Kanae Ando

{"title":"MARK4 enhances stress granule formation under oxidative stress and increases tau accumulation.","authors":"Sho Nakajima, Kotone Watanabe, Grigorii Sultanakhmetov, Aoi Fukuchi, Keiya Ito, Sawako Shimizu, Taro Saito, Akiko Asada, Kanae Ando","doi":"10.1002/2211-5463.70338","DOIUrl":"10.1002/2211-5463.70338","url":null,"abstract":"Overactivation of Microtubule affinity regulating kinase 4 (MARK4) is believed to contribute to Alzheimer's disease pathogenesis. MARK4 promotes the accumulation of the microtubule-binding protein tau, thereby enhancing tau-induced neurodegeneration. However, the underlying mechanisms by which MARK4 enhances tau accumulation are not fully understood. T-cell intracellular antigen 1 (TIA1), a critical regulator of stress granule (SG) formation, has been suggested to initiate tau abnormality. Here, we report that MARK4 and TIA1 synergistically induce stress granule (SG) formation. MARK4 is localized in SGs with TIA1 in mammalian cultured cells and primary neurons. MARK4 suppresses TIA1 dimerization and enhances SG formation under oxidative stress. Co-expression of MARK4 and TIA1 promotes tau accumulation, and knockdown of a fly ortholog of TIA1 suppressed tau toxicity in a Drosophila model. These results identify MARK4 as a novel regulator of SG formation and suggest a mechanistic link between oxidative stress and tau pathology.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Long-term hippocampal alterations and cognitive impairment in a murine model of surgical sepsis 外科败血症小鼠模型的长期海马改变和认知障碍。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-04-16 DOI: 10.1002/2211-5463.70240

Dong Seong Cho, Rebecca Schmitt, Aneesha Dasgupta, Alexandra Ducharme, Jason Doles

{"title":"Long-term hippocampal alterations and cognitive impairment in a murine model of surgical sepsis","authors":"Dong Seong Cho, Rebecca Schmitt, Aneesha Dasgupta, Alexandra Ducharme, Jason Doles","doi":"10.1002/2211-5463.70240","DOIUrl":"10.1002/2211-5463.70240","url":null,"abstract":"Cognitive impairment in sepsis survivors is a growing clinical challenge as the number of sepsis cases rise and acute mortality rates fall. It is estimated that up to 70% of sepsis patients experience cognitive dysfunction and many report persistent dysfunction post-sepsis. Cognitive impairment is a broad term that refers to sepsis-associated brain dysfunction or encephalopathy (SABD or SAE, respectively). While many contributors, such as inflammation, blood–brain barrier dysfunction, and extended microglial activation are implicated in SABD/SAE development, much is still unknown regarding the underlying mechanistic causes of persistent cognitive defects in sepsis survivors. Here, we employed cecal ligation and puncture (CLP) to model surgical sepsis in mice, after which mice were subjected to multiple memory function assays for up to 2 months post-sepsis. Furthermore, single-cell RNA sequencing and validation studies were performed with murine hippocampi to query alterations in the brain microenvironment. Our study shows that CLP mice exhibited decreased spontaneous alternation at 4 weeks and decreases in both short- and long-term recognition (at 6 weeks and 2 weeks, respectively) accompanied by substantially altered cell type makeup of the hippocampus, including hippocampal neuron and pericyte loss. Finally, transcriptional alterations in the macrophage populations implicate aberrant activation in CLP survivors. In conclusion, post-sepsis mice exhibit reduced memory capacity and altered hippocampal cell composition and transcriptional profiles. This study and associated data set will be valuable for further investigation of the underlying pathophysiology of SABD/SAE and elucidation of potential therapeutic candidates.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1657-1668"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Acute caffeine treatment protects the developing retina from ischemia-induced cell death 急性咖啡因治疗可保护发育中的视网膜免受缺血引起的细胞死亡。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-05-13 DOI: 10.1002/2211-5463.70251

Amanda Alves Nascimento, Danniel Pereira-Figueiredo, Gabriella Grossi de Lima Dias, Gabriel Ferreira dos Santos, Mariana Rodrigues Pereira, Rafael Brito, Karin C Calaza

{"title":"Acute caffeine treatment protects the developing retina from ischemia-induced cell death","authors":"Amanda Alves Nascimento, Danniel Pereira-Figueiredo, Gabriella Grossi de Lima Dias, Gabriel Ferreira dos Santos, Mariana Rodrigues Pereira, Rafael Brito, Karin C Calaza","doi":"10.1002/2211-5463.70251","DOIUrl":"10.1002/2211-5463.70251","url":null,"abstract":"Ischemic damage to the retina during development can lead to irreversible neuronal loss, driven in part by excitotoxic mechanisms and energy deprivation. While two-day caffeine exposure has previously been shown to confer neuroprotection in this context, it remained unclear whether acute administration during an ischemic event could yield similar benefits. In this study, we used an ex vivo model of oxygen and glucose deprivation (OGD) in chick embryo retinas to investigate whether a single, acute dose of caffeine applied during the insult reduces cell death and engages intracellular survival pathways. Results showed a significant reduction in OGD-induced cytotoxicity by caffeine exposure. However, unlike in the context of chronic exposure, acute caffeine exposure did not increase BDNF expression. Furthermore, antioxidant agents failed to mimic caffeine's protective effects, and acute caffeine exposure did not induce the expression of antioxidant response genes, nor oxidative stress or VEGF expression, suggesting that oxidative stress mitigation is not the primary mechanism for this effect. However, pharmacological antagonism of adenosine A2A receptors with ZM241385 reproduced the neuroprotective effects of caffeine and reduced extracellular glutamate levels during OGD. These findings indicate that acute caffeine administration protects the developing retina primarily through A2A receptor antagonism and inhibition of glutamate excitotoxicity, rather than by activating canonical survival signaling pathways. This supports the potential use of caffeine as a rapid neuroprotective agent during acute ischemic events in the immature central nervous system.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1726-1740"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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