Biochemical and biophysical research communications最新文献_第6页

Mitochondrial-targeting strategies with homoharringtonine: A novel approach for chemoresistant rectal cancer.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-05 DOI: 10.1016/j.bbrc.2024.151141

Hu Chenghao, Liu Xuefeng, Pang Junli, Wang Ke, Li Haixia, Hu Guangyue, Luo Qingqin, Wu Feng

{"title":"Mitochondrial-targeting strategies with homoharringtonine: A novel approach for chemoresistant rectal cancer.","authors":"Hu Chenghao, Liu Xuefeng, Pang Junli, Wang Ke, Li Haixia, Hu Guangyue, Luo Qingqin, Wu Feng","doi":"10.1016/j.bbrc.2024.151141","DOIUrl":"10.1016/j.bbrc.2024.151141","url":null,"abstract":"5-Fluorouracil (5-FU) resistance poses a significant challenge in the treatment of rectal cancer, driving the need for novel therapeutic strategies. In this study, we established 5-FU-resistant rectal cancer cell lines (SW837-r, SNU-C1-r) and identified homoharringtonine (HHT) as a potent and selective anticancer agent through high-throughput drug screening of 291 compounds. HHT displayed the highest selective drug sensitivity score (sDSS), showing strong activity against resistant cells while sparing normal rectal epithelial cells. Further investigations revealed that 5-FU-resistant cells exhibited enhanced mitochondrial biogenesis and function compared to normal cells, and HHT exerted its cytotoxic effects by targeting mitochondrial respiration. HHT significantly reduced oxygen consumption rate (OCR), mitochondrial complex I activity, and ATP production in resistant cells, with mitochondrial respiration-deficient ρ0 cells showing reduced sensitivity to HHT. In vivo, HHT alone reduced tumor growth by 60 % in the resistant xenograft model. In the sensitive xenograft model, combination therapy with 5-FU achieved an 85 % reduction in tumor volume compared to controls, with tumors in the combination group displaying minimal regrowth. These results demonstrate that HHT effectively targets mitochondrial function in resistant rectal cancer cells and, in combination with 5-FU, offers synergistic antitumor effects and prolonged tumor suppression. The favorable safety profile of HHT further highlights its potential as a promising therapeutic agent for overcoming 5-FU resistance in rectal cancer.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151141"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833766","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

1,25(OH)2D3 promotes insulin secretion through the classical pyroptosis pathway in vitro and vivo.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1016/j.bbrc.2024.151058

Yuxuan Zheng, Zhihao Wu, Xun Wei, Lewen Zhang, Yudie Hu, Zhengyu Zhou

{"title":"1,25(OH)2D3 promotes insulin secretion through the classical pyroptosis pathway in vitro and vivo.","authors":"Yuxuan Zheng, Zhihao Wu, Xun Wei, Lewen Zhang, Yudie Hu, Zhengyu Zhou","doi":"10.1016/j.bbrc.2024.151058","DOIUrl":"10.1016/j.bbrc.2024.151058","url":null,"abstract":"Background: Diabetes is a chronic metabolic disorder characterized by persistently elevated levels of blood glucose. Research has demonstrated a close relationship between inflammation and the development of diabetes. Vitamin D has been shown to be significantly associated with type 2 diabetes; however, the mechanisms by which it regulates inflammation during the onset of the disease remain incompletely understood. In this study, we investigated the effect of pyroptosis on pancreatic β-cell function in diabetes and explored the role of 1,25(OH)2D3 in type 2 diabetes through the pyroptosis signaling pathway.Methods: In both in vivo and in vitro settings, we established a diabetes model combined with 1,25(OH)₂D₃ intervention to investigate its impact on insulin secretion levels, the release of inflammatory factors, and the expression levels of pyroptosis-related proteins.Results: In both in vivo and in vitro experiments, we have observed that 1,25(OH)₂D₃ exhibits anti-inflammatory properties by downregulating the expression levels of pyroptosis-related proteins. Furthermore, it provides protection against pancreatic β-cell damage caused by type 2 diabetes mellitus (T2DM) and enhances insulin secretion. Inhibition of gasdermin D (GSDMD) expression impedes the progression of cell pyroptosis, reduces the amplification of the inflammatory response, and protects pancreatic cells from injury.Conclusion: We hypothesize that the induction of pancreatic cells through pyroptosis occurs via the classical pathway in T2DM, and propose that 1,25(OH)2D3 may have a beneficial effect on this process. Consequently, 1,25(OH)2D3 could potentially serve as an adjuvant to inhibit the pyroptosis of pancreatic β cells by targeting the classical signaling pathway, thereby reducing the inflammatory response and alleviating symptoms associated with diabetes.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151058"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791040","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

ALKBH5 deletion ameliorates inflammation by regulating IRF3 signaling in an m⁶A-dependent manner after myocardial infarction.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-20 DOI: 10.1016/j.bbrc.2024.151039

Xiuye Zhao, Zhen Liang, Wei Zhao, Yiping Tao, Yan Hao, Yunqi Liu, Jiapan Wang, Jie Yu, Hongyu Ji, Huiwei Jiang, Silun Xu, Jintao Gu, Ye Yuan, Zhimin Du

{"title":"ALKBH5 deletion ameliorates inflammation by regulating IRF3 signaling in an m6A-dependent manner after myocardial infarction.","authors":"Xiuye Zhao, Zhen Liang, Wei Zhao, Yiping Tao, Yan Hao, Yunqi Liu, Jiapan Wang, Jie Yu, Hongyu Ji, Huiwei Jiang, Silun Xu, Jintao Gu, Ye Yuan, Zhimin Du","doi":"10.1016/j.bbrc.2024.151039","DOIUrl":"10.1016/j.bbrc.2024.151039","url":null,"abstract":"AlkB homolog 5 (ALKBH5) plays an important role in ischemia/reperfusion (I/R), cardiac hypertrophy and other cardiovascular diseases (CVDs). However, whether ALKBH5 regulates the inflammatory response by mediating M1/M2 macrophage conversion after myocardial infarction (MI) is unclear. In this study, we found that ALKBH5 protein expression was significantly downregulated in MI mice. To investigate the role of ALKBH5 in the inflammatory response after MI, we assessed the expression of interleukin-6 (Il-6), interleukin-1β (Il-1β), tumor necrosis factor-α (Tnf-α) and interferon-Ⅰ (Ifn-Ⅰ) by qRT‒PCR and found that ALKBH5 knockout improved cardiac function, reduced pro-inflammatory cytokine release and decreased cardiomyocyte apoptosis. In addition, the knockdown of ALKBH5 significantly inhibited the release of pro-inflammatory cytokines and the migration of RAW264.7 macrophages treated with lipopolysaccharide (LPS). Mechanistically, our results suggested that ALKBH5 potentially recognized the m6A binding site on interferon regulatory factor 3 (IRF3) and regulated the IRF3 expression to influence macrophage M1/M2 phenotypic transition and inflammatory cytokine release. In conclusion, our results indicated that ALKBH5 ablation inhibited inflammation by regulating the transcription of IRF3. This study provides new insights into the clinical management of the inflammatory response after MI.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151039"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791042","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

Sialidase NEU3 silencing inhibits angiogenesis of EA.hy926 cells by regulating Wnt/β-catenin signaling pathway. 沉默Sialidase NEU3可通过调节Wnt/β-catenin信号通路抑制EA.hy926细胞的血管生成。

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-30 DOI: 10.1016/j.bbrc.2024.151098

Yilun Wu, Xin Yuan, Yi Zhang, Fang Ma, Wei Zhao, Xinrui Sun, Xue Ma, Yingjiao Chen

{"title":"Sialidase NEU3 silencing inhibits angiogenesis of EA.hy926 cells by regulating Wnt/β-catenin signaling pathway.","authors":"Yilun Wu, Xin Yuan, Yi Zhang, Fang Ma, Wei Zhao, Xinrui Sun, Xue Ma, Yingjiao Chen","doi":"10.1016/j.bbrc.2024.151098","DOIUrl":"10.1016/j.bbrc.2024.151098","url":null,"abstract":"Angiogenesis significantly drives tumor progression, and the functions of vascular endothelial cells are influenced by various factors. Tumor cells are characterized by abnormal sialylation, and their dynamic balance depends on sialyltransferases and sialidases. NEU3 is a plasma membrane-associated sialidase, vital for the regulation of cell surface sialylation. Our study revealed that, NEU3 is the most abundantly expressed among the four sialidase subtypes in EA.hy926 cells. Silencing NEU3 expression resulted in cell apoptosis and reduced proliferation, highlighting its crucial function in the regulation of cell activity. Subsequent experiments using transwell and tube formation assays demonstrated that the inhibition of NEU3 expression suppressed cell migration and angiogenesis. RNA sequencing analysis further elucidated that altering NEU3 expression in EA.hy926 cells impacts the Wnt/β-Catenin signaling pathway and c-Myc levels, thereby modulating cellular survival and migration capacity and exerting a regulatory effect on angiogenesis. These findings suggest that targeting NEU3 in the vascular endothelium may represent a promising strategy for anti-angiogenic therapy in tumors.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151098"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821860","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 effect of platelet-derived growth factor-aa (PDGFA) conjugated with low-molecular-weight protamine (LMWP) on hair loss improvement effect.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI: 10.1016/j.bbrc.2024.151110

Seo Yeon Shin, Nu Ri Song, Dai Hyun Jung, Su Jung Kim, Kyung Mok Park

引用次数: 0

Starvation changes the pre-rRNA accumulations in Caenorhabditis elegans.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-09 DOI: 10.1016/j.bbrc.2024.151125

Shahriar Rahman Shovon, Tomoki Uematsu, Yuki Osaki, Tatsushi Masui, Takashi Koyama, Toshinobu Fujiwara, Chisato Ushida

{"title":"Starvation changes the pre-rRNA accumulations in Caenorhabditis elegans.","authors":"Shahriar Rahman Shovon, Tomoki Uematsu, Yuki Osaki, Tatsushi Masui, Takashi Koyama, Toshinobu Fujiwara, Chisato Ushida","doi":"10.1016/j.bbrc.2024.151125","DOIUrl":"10.1016/j.bbrc.2024.151125","url":null,"abstract":"The precursor rRNA (pre-rRNA) processing pathway in Caenorhabditis elegans remains unidentified. We have determined the cleavage site within the internal transcribed spacer 2, which generates pre-rRNA f of 5.8S rRNA and pre-rRNA g of 26S rRNA. Ribosome biogenesis is the most energetically demanding process of the cell. Under starved conditions, cells conserve energy by reconfiguring ribosome biogenesis to sustain proper growth. We investigated the short-term effects of starvation on the ribosomal RNA (rRNA) maturation in C. elegans. Northern blot analysis revealed significant changes in both small and large pre-rRNAs, with a substantial decrease in pre-rRNA c'1/27SA2 of the large subunit and an increase in pre-rRNA d of the small subunit. Additionally, most pre-rRNAs accumulated in the nucleolar center, while the rRNA maturation factor FIB-1 accumulated at the nucleolar periphery. Nutritional replenishment restored the pre-rRNA accumulation pattern and the distribution of pre-rRNAs in the nucleolus to pre-starvation conditions.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151125"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805838","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

Therapeutic potential of silica nanoparticles, cisplatin, and quercetin on ovarian cancer: In vivo model.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI: 10.1016/j.bbrc.2024.151121

Laiba Saeed, Sumera Sajjad, Muhammad Zubair, Farhat Jabeen

{"title":"Therapeutic potential of silica nanoparticles, cisplatin, and quercetin on ovarian cancer: In vivo model.","authors":"Laiba Saeed, Sumera Sajjad, Muhammad Zubair, Farhat Jabeen","doi":"10.1016/j.bbrc.2024.151121","DOIUrl":"10.1016/j.bbrc.2024.151121","url":null,"abstract":"The present study evaluated the effect of silica nanoparticles, quercetin, and cisplatin against ovarian cancer. Cisplatin is a potent antineoplastic agent but has greater toxicity against cancer. Quercetin is a powerful flavonoid with remarkable anti-cancer activity due to its anti-apoptotic nature. Forty female albino rats were randomly divided into eight groups, with five rats per group. Group 1 (G1) was normal control, G2 received Carboxymethylcellulose; G3 was the normal control and treated with quercetin, G4 was given silica nanoparticles, G5 was treated with cisplatin. G6 was the tumor control. Tumor induction was done by 7, 12-dimethylbenz (a) anthracene (DMBA), G7 was treated with quercetin-cisplatin-silica nanoparticles, and in G8 quercetin-cisplatin silica nanoparticles were used to treat the induced tumor. Chemically synthesized silica nanoparticles were characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and Fourier Transform Infrared (FTIR). After the treatment, animals were sacrificed and tested for biochemical and hormonal assays. G6 displayed increased body weight and a significant rise in CA125 as compared to G1. G6 also exhibited an altered hormonal profile, with a particular increase in estrogen, FSH, and testosterone, along with reduced LH and progesterone levels. Lipid profile, liver enzymes, and renal parameters (urea and creatinine) increased in G6, but G8 significantly ameliorated all damaging effects of DMBA as observed in G6. The current study revealed that silica nanoparticles combined with cisplatin and quercetin demonstrated greater protection against drastic changes induced by carcinogens in ovarian cancer mice models.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151121"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805877","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

Estimating the structural and spatial variables of allantoinase enzyme critical for protein adsorption.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-10 DOI: 10.1016/j.bbrc.2024.151161

Sheetal Das, Janarthanan Krishnamoorthy, Rajiv K Kar

{"title":"Estimating the structural and spatial variables of allantoinase enzyme critical for protein adsorption.","authors":"Sheetal Das, Janarthanan Krishnamoorthy, Rajiv K Kar","doi":"10.1016/j.bbrc.2024.151161","DOIUrl":"10.1016/j.bbrc.2024.151161","url":null,"abstract":"Designing enzyme-based sensors necessitates a comprehensive exploration of macromolecular properties. Integrating enzymes with a suitable transducer involves immobilizing them onto a surface, facilitated through adsorption or entrapment techniques. Allantoin, a stable biomarkers metabolite, holds promise for detecting oxidative stress-related complications through its enzyme. In this study, we examined allantoinase from various taxa, with bacterial origin comprising over 70 % of the dataset. Crucial residues such as Asp, His, and Gly in the active binding site and associated hydrophobic area play a critical role in maintaining binding specificity and sensitivity. In this work, we utilized bioinformatics tools to analyze properties such as pI, solubility index, amino acid hydropathy, stability, disordered regions, solvent-accessible surface area, and hydrodynamic parameters. The stability of allantoinase is assessed through surface Cys residues, hydrophobicity, and thermostability. Furthermore, the compactness and spherical geometry of the enzyme, which are crucial for protein adsorption are evaluated through parameters like spatial conformation, asphericity, and hydrodynamic radius distribution. Among the dataset, bacterial allantoinase demonstrates significant adaptability to environmental changes, as indicated by solvent-accessible surface area and instability index. This study highlights the importance of macromolecular properties underscoring their significance in optimizing, calibrating, and ensuring the stability of enzyme-based sensor design.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151161"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852202","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

MDM2 up-regulates the energy metabolism in NSCLC in a p53-independent manner.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI: 10.1016/j.bbrc.2024.151169

Elizaveta Fefilova, Yulia Kirdeeva, Sergey Parfenyev, Alexandra Daks, Olga Fedorova, Margarita Sorokina, Nguyen Xuan Ha, Tran Thu Huong, Vu Thanh Loc, Pham The Hai, Nguyen Manh Cuong, Nickolai Barlev, Oleg Shuvalov

{"title":"MDM2 up-regulates the energy metabolism in NSCLC in a p53-independent manner.","authors":"Elizaveta Fefilova, Yulia Kirdeeva, Sergey Parfenyev, Alexandra Daks, Olga Fedorova, Margarita Sorokina, Nguyen Xuan Ha, Tran Thu Huong, Vu Thanh Loc, Pham The Hai, Nguyen Manh Cuong, Nickolai Barlev, Oleg Shuvalov","doi":"10.1016/j.bbrc.2024.151169","DOIUrl":"10.1016/j.bbrc.2024.151169","url":null,"abstract":"Although an E3 ligase MDM2 is the major negative regulator of the p53 tumor suppressor, a growing body of evidence suggests its p53-independent oncogenic properties. In particular, MDM2 has been shown to regulate serine metabolism independently of p53 status in several types of neoplasia, including NSCLC. Using the GSEA approach and publicly available molecular data on NSCLC tumors, our bioinformatics data suggest that MDM2 affects a number of metabolic genes, particularly those encoding components of the electron transport chain (ETC). To experimentally elucidate the role of MDM2 in respiration and energy metabolism of NSCLC cell models, we established NSCLC cell lines (WT p53+ A549 and p53-null H1299) overexpressing wild-type MDM2, or its catalytically deficient (C464A) mutant (MUT), or the control vector. Using TMRE staining and SeaHorse energy profiling, we demonstrated that wild-type MDM2, but not its catalytically inactive mutant, significantly increased mitochondrial membrane potential (MMP), glycolysis, respiration, and ATP production in a p53-independent manner. Further, we compared MDM2-associated effects of two natural compounds that, according to our docking experiment data, bind MDM2 with affinities similar to nutlin-3A, ganoderic acid A and berberine. Despite the fact that both nutlin-3A and berberine stabilized the MDM2 protein, they displayed differential effects on energy metabolism. Taken together, our data argue that MDM2 affects energy metabolism likely in a p53-independent manner. These results also highlight another pharmacological dimension of using MDM2-targeting compounds as potent inhibitors of glycolysis and respiration in tumor cells.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151169"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852285","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

Neuroprotective effects of activated fibroblast growth factor receptor 1 via the suppression of p53 accumulation against poly-PR-mediated toxicity.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-13 DOI: 10.1016/j.bbrc.2024.151181

Taisei Ito, Kazuki Ohuchi, Hisaka Kurita, Takanori Murakami, Shinnosuke Takizawa, Ayaka Fujimaki, Junya Murata, Yasuhisa Oida, Isao Hozumi, Kiyoyuki Kitaichi, Masatoshi Inden

{"title":"Neuroprotective effects of activated fibroblast growth factor receptor 1 via the suppression of p53 accumulation against poly-PR-mediated toxicity.","authors":"Taisei Ito, Kazuki Ohuchi, Hisaka Kurita, Takanori Murakami, Shinnosuke Takizawa, Ayaka Fujimaki, Junya Murata, Yasuhisa Oida, Isao Hozumi, Kiyoyuki Kitaichi, Masatoshi Inden","doi":"10.1016/j.bbrc.2024.151181","DOIUrl":"10.1016/j.bbrc.2024.151181","url":null,"abstract":"A GGGGCC hexanucleotide repeat expansion (HRE) within the C9orf72 gene is a major causative factor in amyotrophic lateral sclerosis (ALS). This aberrant HRE results in the generation of five distinct dipeptide repeat proteins (DPRs). Among the DPRs, poly-PR accumulates in the nucleus and exhibits particularly strong toxicity to motor and cortical neurons. Fibroblast growth factor receptor 1 (FGFR1) is known to promote neurogenesis and inhibit apoptosis in neurons. Nevertheless, there has been no previous report of its neuroprotective effects against poly-PR toxicity. The objective of this study was to investigate the neuroprotective effects of FGFR1 activation in poly-PR-expressing NSC34 motor neuron-like cells. RT-qPCR analysis in NSC34 cells showed that Fgfr1 was the most highly expressed member of the Fgfr family in NSC34 cells. The activation of FGFR1 by FGF2, a common ligand for all FGFRs, exerted neuroprotective effects against the toxicity of poly-PR. Additionally, FGFR1 activation was observed to enhance cell viability through the PI3K-AKT pathway, while the contribution of the MEK-ERK pathway was found to be limited. Furthermore, FGFR1 activation suppressed the accumulation of p53 protein and promoted its degradation through increased murine double minute 2 (MDM2), an E3 ubiquitin ligase that targets p53. The neuroprotective effects were attenuated by PD173074, a selective FGFR1 inhibitor or Nutlin-3a, an inhibitor of the p53-MDM2 interaction. Overall, these findings suggest that FGFR1 activation provides neuroprotection against poly-PR toxicity. Consequently, this study suggests the potential utility of FGFR1 activation as a therapeutic strategy for ALS.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151181"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852286","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