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Co-treatment with melatonin and ortho-topolin riboside exhibits anti-proliferation activity in radioresistant MDA-MB-231 cells by altering metabolic and transcriptomic profiles. 褪黑素和原东莨菪碱核苷联合治疗可通过改变新陈代谢和转录组特征,在抗放射MDA-MB-231细胞中显示出抗增殖活性。
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-06 DOI: 10.1016/j.bbrc.2024.151132
Soon-Wook Noh, Dae Kyeong Kim, Seung Min Nam, Jungmin Yeu, Seungcheol Lee, Ji-Won Lee, Somi Kim Cho, Hyung-Kyoon Choi
{"title":"Co-treatment with melatonin and ortho-topolin riboside exhibits anti-proliferation activity in radioresistant MDA-MB-231 cells by altering metabolic and transcriptomic profiles.","authors":"Soon-Wook Noh, Dae Kyeong Kim, Seung Min Nam, Jungmin Yeu, Seungcheol Lee, Ji-Won Lee, Somi Kim Cho, Hyung-Kyoon Choi","doi":"10.1016/j.bbrc.2024.151132","DOIUrl":"10.1016/j.bbrc.2024.151132","url":null,"abstract":"<p><p>Radiation therapy represents the primary treatment option for triple-negative breast cancer. However, radio resistance is associated with a poor prognosis and an increased risk of recurrence. Radioresistant MDA-MB-231 cells, a radioresistant triple-negative breast cancer cell line, were co-treated with ortho-topolin riboside and melatonin. The energy metabolism, metabolic profile, and transcriptomic profile of these cells were studied using XFe, gas chromatography, and next-generation sequencing. The combination treatment simultaneously inhibited glycolysis and mitochondrial respiration and inhibited the glycolytic transport chain by decreasing ATP5MC1 and ATP5ME1 gene expression, which synthesize ATP synthase, resulting in a decrease in aspartate, a precursor to pyrimidine. Furthermore, reduced CDA and NME1 gene expression impeded pyrimidine metabolism. Conversely, augmented AKR1C2 and AKR1C3 expression and elevated CDKN1A expression, which synthesizes p21, curtailed cell proliferation. Additionally, diminished TSNAX-DISC1 and CYP1B1 expression similarly restrained cell proliferation, potentially by reducing Wnt/β-catenin signaling. These findings may represent a novel therapeutic approach for patients with radioresistant triple-negative breast cancer.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151132"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817098","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
Antimicrobial peptide Mt 5 inhibits human hepatocellular carcinoma cell HepG2 proliferation.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-07 DOI: 10.1016/j.bbrc.2024.151126
Yanping Shi, Ye Zeng, Ruifeng Zuo, Shenghua Wu, Lihua Zhang, Yingchun Zhang, Tao Wang
{"title":"Antimicrobial peptide Mt 5 inhibits human hepatocellular carcinoma cell HepG2 proliferation.","authors":"Yanping Shi, Ye Zeng, Ruifeng Zuo, Shenghua Wu, Lihua Zhang, Yingchun Zhang, Tao Wang","doi":"10.1016/j.bbrc.2024.151126","DOIUrl":"10.1016/j.bbrc.2024.151126","url":null,"abstract":"<p><p>The Mt 5 peptide is an antimicrobial peptide, its effect on hepatocellular carcinoma (HCC) and its underlying mechanism is not understood. Therefore, this study aimed to investigate the effects of the Mt 5 peptide in a human HCC cell line, namely HepG2, in vitro. Notably, Mt 5 markedly reduced the growth of HepG2 cells by disrupting the cell membrane while exhibiting minimal toxicity to healthy liver cells. Furthermore, Mt 5 treatment increased intracellular reactive oxygen species levels and decreased the mitochondria membrane potential, suggesting the induction of mitochondrial damage-mediated apoptosis. Additionally, Mt 5-mediated cytoskeleton disruption suggested the potential inhibition of cell metastasis. Altogether, the findings of this study indicate the potential of the Mt 5 peptide as a drug candidate against HCC.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151126"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794229","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
Combined PD-1 and IL-10 blockade reinvigorates mucosal CD8+T exhaustion and relieves liver damage after intestinal ischemia reperfusion attack.
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.2024.151137
Zi-Meng Liu, Yi-Nan Zhang, Hu-Fei Zhang, Xu-Yu Zhang
{"title":"Combined PD-1 and IL-10 blockade reinvigorates mucosal CD8<sup>+</sup>T exhaustion and relieves liver damage after intestinal ischemia reperfusion attack.","authors":"Zi-Meng Liu, Yi-Nan Zhang, Hu-Fei Zhang, Xu-Yu Zhang","doi":"10.1016/j.bbrc.2024.151137","DOIUrl":"10.1016/j.bbrc.2024.151137","url":null,"abstract":"<p><p>Currently, impairments in gut mucosal immunity following intestinal ischemia reperfusion (IR) remain unclear. Mucosal CD8<sup>+</sup>T cells are critical for host defense against bacterial translocation from the gut lumen, and exhausted T cells lose robust effector functions. The present study was designed to verify the hypothesis that intestinal IR leads to mucosal CD8<sup>+</sup>T cell exhaustion, and that reinvigoration of exhausted CD8<sup>+</sup>T cell attenuates IR-induced bacterial translocation and liver damage. The intestinal IR model was performed through clamping the superior mesenteric artery in mice. The percent of exhausted CD8<sup>+</sup>T cells and the effector function of CD8<sup>+</sup>T cells were examined to determine the occurrence of intestinal mucosal CD8<sup>+</sup>T cell exhaustion. Subsequently, PD-1 blockade or combined PD-1 and IL-10 blockade was respectively used to reinvigorate exhausted CD8<sup>+</sup>T cells. Serum biomarkers, bacterial RNA and colonies, and inflammatory factors were examined to determine bacterial translocation and liver damage. The results indicated that intestinal IR induced CD8<sup>+</sup>T cell exhaustion in mucosal tissues, as evidenced by increased PD-1<sup>+</sup> and PD-1<sup>+</sup>LAG-3<sup>+</sup>CD8<sup>+</sup>T cells and decreased IL-2 and TNF-α expression in CD8<sup>+</sup>T cells. Combined PD-1 and IL-10 blockade, but not PD-1 blockade alone, reinvigorated CD8<sup>+</sup>T cell exhaustion, as evidenced by increased generation of exhausted CD8<sup>+</sup>T cells with cytotoxicity and effector function, and elevated production of IFN-γ. Moreover, combined blockade significantly reduced the translocation of gut bacteria and injury to the liver after IR. In conclusion, intestinal IR leads to mucosal CD8<sup>+</sup>T cell exhaustion. Combined PD-1 and IL-10 blockade reinvigorates exhausted CD8<sup>+</sup>T cells, and ameliorates bacterial translocation and liver damage following IR.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151137"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794231","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
Excitatory-inhibitory synaptic imbalance induced by acute intra-hippocampus injections of amyloid-β oligomers.
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.2024.151133
Jorge Arriagada, Daymara Mercerón, Álvaro Ardiles, Pablo Muñoz, Andrea Paula-Lima
{"title":"Excitatory-inhibitory synaptic imbalance induced by acute intra-hippocampus injections of amyloid-β oligomers.","authors":"Jorge Arriagada, Daymara Mercerón, Álvaro Ardiles, Pablo Muñoz, Andrea Paula-Lima","doi":"10.1016/j.bbrc.2024.151133","DOIUrl":"10.1016/j.bbrc.2024.151133","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by the accumulation of soluble amyloid-β oligomers (AβOs) in the brain, which disrupt synaptic function and promote cognitive decline. Here, we investigated the effects of AβOs on excitatory and inhibitory synaptic transmission and plasticity by performing stereotaxic injections of AβOs directly into the hippocampal CA1 region, followed by hippocampal slice isolation for electrophysiological measurements. AβOs injections altered basal excitatory synaptic transmission, reducing field excitatory postsynaptic potentials (fEPSPs) and impairing excitatory long-term potentiation (LTP). Additionally, AβOs injections significantly increased basal inhibitory synaptic transmission, as evidenced by the increased amplitude of field inhibitory postsynaptic potentials (fIPSPs), but impaired the induction and maintenance of inhibitory long-term potentiation (iLTP). Accordingly, we propose that AβOs injections induce the saturation of the GABAergic system and thus disrupt the hippocampal excitatory-inhibitory balance. These findings highlight the dual impact of AβOs on both excitatory and inhibitory synapses, generating synaptic dysregulation and possibly worsening cognitive decline in AD. Understanding these mechanisms could provide new insights for developing therapies to restore synaptic balance and hippocampal function in AD.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151133"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806128","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
Generation of chimeric antigen receptor-macrophages by using human induced pluripotent stem cells. 利用人类诱导多能干细胞生成嵌合抗原受体-巨噬细胞。
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.2024.151158
Kenji Kitajima, Takahiko Hara
{"title":"Generation of chimeric antigen receptor-macrophages by using human induced pluripotent stem cells.","authors":"Kenji Kitajima, Takahiko Hara","doi":"10.1016/j.bbrc.2024.151158","DOIUrl":"10.1016/j.bbrc.2024.151158","url":null,"abstract":"<p><p>Cancer immunotherapy using chimeric antigen receptor (CAR) cells shows high therapeutic efficacy against several types of leukemia. Among acute lymphoblastic leukemias (ALLs), B cell-derived ALL can be cured by CAR-expressing T cells (CAR-Ts); however, CAR-T cells cannot be simply applied for T cell-derived ALL (T-ALL) because antigens expressed by T-ALL cells, but not by CAR-T cells, have not yet been identified. To apply CAR-T therapy for T-ALL, gene editing of CAR-T cells is required to avoid attacking CAR-T cells themselves. Alternatively, CAR-expressing macrophages (CAR-Ms) have proven to be effective against various cancers, suggesting that CAR-Ms may also be effective against T-ALL. Recently, we developed an efficient differentiation induction system to generate a large number of macrophages from human induced pluripotent stem cells (iPSCs). Here, we asked whether these human iPSC-derived macrophages (iPS-MACs) can be used to develop and evaluate CAR-based immunotherapy against T-ALLs. When non-transduced iPS-MACs were co-cultured with human T-ALL-derived cells, the iPS-MACs appeared to phagocytose parts of T-ALL cells; this method of phagocytosis operated mainly through incorporation of small, \"bite-sized\" vesicles derived from the T-ALL cells into iPS-MACs (similar to trogocytosis). By contrast, when CAR-expressing iPS-MACs were co-cultured with T-ALL cells, iPS-MACs engulfed the whole T-ALL cell. Thus, our differentiation induction system may be a promising tool for building up CAR-M therapy for T-ALLs.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151158"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823694","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
Time-resolved fluorescence of ANS dye as a sensor of proteins LLPS.
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.2024.151164
Sergey A Silonov, Semen V Nesterov, Anastasia A Gavrilova, Olga S Sergeeva, Anna E Romanovich, Irina M Kuznetsova, Konstantin K Turoverov, Alexander V Fonin
{"title":"Time-resolved fluorescence of ANS dye as a sensor of proteins LLPS.","authors":"Sergey A Silonov, Semen V Nesterov, Anastasia A Gavrilova, Olga S Sergeeva, Anna E Romanovich, Irina M Kuznetsova, Konstantin K Turoverov, Alexander V Fonin","doi":"10.1016/j.bbrc.2024.151164","DOIUrl":"10.1016/j.bbrc.2024.151164","url":null,"abstract":"<p><p>The explosive growth in the number of works addressing the phase separation of intrinsically disordered proteins has driven both the development of new approaches and the optimization of existing methods for biomolecular condensate visualization. In this work, we studied the potential use of the fluorescent dye ANS as a sensor for liquid-liquid phase separation (LLPS), focusing on visualizing condensates formed by the stress-granules scaffold protein G3BP1. Using fluorescence lifetime imaging microscopy (FLIM), we demonstrated that ANS can accumulate in RNA-induced G3BP1 condensates in aqueous solutions, but not in G3BP1 condensates formed under macromolecular crowding conditions in highly concentrated PEG solutions. We showed that the experimentally determined limiting fluorescence anisotropy (r<sub>0</sub>'), which characterizes the amplitude of high-frequency intramolecular mobility of ANS in aqueous solutions containing RNA-induced G3BP1 condensates, is half the value observed for ANS in aqueous G3BP1 solutions. Our results demonstrate the feasibility of using time-resolved fluorescence spectroscopy and microscopy of ANS for detecting LLPS of intrinsically disordered proteins in aqueous solutions.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151164"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823769","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
Lipid mediator palmitoylethanolamide (PEA) inhibits pathogenic T cell differentiation in vitro and in vivo. 脂质介质棕榈酰乙醇酰胺(PEA)可在体外和体内抑制致病性 T 细胞分化。
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1016/j.bbrc.2024.151085
Yasuhiro Soga, Naganori Kamiyama, Takashi Ozaki, Thanyakorn Chalalai, Nozomi Sachi, Sotaro Ozaka, Yomei Kagoshima, Supanuch Ekronarongchai, Masahiro Yamamoto, Takashi Kobayashi
{"title":"Lipid mediator palmitoylethanolamide (PEA) inhibits pathogenic T cell differentiation in vitro and in vivo.","authors":"Yasuhiro Soga, Naganori Kamiyama, Takashi Ozaki, Thanyakorn Chalalai, Nozomi Sachi, Sotaro Ozaka, Yomei Kagoshima, Supanuch Ekronarongchai, Masahiro Yamamoto, Takashi Kobayashi","doi":"10.1016/j.bbrc.2024.151085","DOIUrl":"10.1016/j.bbrc.2024.151085","url":null,"abstract":"<p><p>Lipid mediator, palmitoylethanolamide (PEA) has recently attracted attention as a potential therapeutic option for various inflammatory autoimmune diseases. It has been reported that PEA exerts an inhibitory effect on inflammation triggered by PRRs, particularly Toll-like receptors expressed on myeloid antigen-presenting cells. However, the precise role of PEA in T cell development and function has not yet been elucidated. Here, we found that PEA suppressed the differentiation of Type 1 T helper (Th1) cells and Th17 cells, which are known to cause autoimmune diseases, as well as Th2 cells, which are associated with allergic diseases. This suppression occurs by inhibiting the expression of the master transcription factors crucial for their differentiation in vitro. Notably, PEA had no impact on the process of differentiating regulatory T cells, which play a crucial role in preventing the onset of autoimmune diseases. To further confirm the effect of PEA in vivo, we administered PEA to a Toxoplasma gondii infection model and an ovalbumin-induced allergic rhinitis model. Mice infected with T. gondii, in which Th1 responses are important for pathogen eradication, exhibited enhanced susceptibility. Mice with allergic rhinitis, where Th2 responses contribute to an exacerbation of symptoms, showed alleviated symptoms. Collectively, these findings suggest that PEA has potential applications as a new therapeutic agent for inflammatory autoimmune and allergic diseases based on excessive T cell activity.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151085"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845671","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
LXRα agonist differentially regulates BAFF expression and biological effects in RAW264.7 cells depending on growth status: LXRα activation and BAFF signaling in RAW264.7 cells.
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.2024.151067
Yisa Teng, Haiyan Xu, Xiaozhou He, Qianfeng Zhuang, Hao Lu, Renfang Xu, Dong Xue
{"title":"LXRα agonist differentially regulates BAFF expression and biological effects in RAW264.7 cells depending on growth status: LXRα activation and BAFF signaling in RAW264.7 cells.","authors":"Yisa Teng, Haiyan Xu, Xiaozhou He, Qianfeng Zhuang, Hao Lu, Renfang Xu, Dong Xue","doi":"10.1016/j.bbrc.2024.151067","DOIUrl":"10.1016/j.bbrc.2024.151067","url":null,"abstract":"<p><p>B- cell-activating factor (BAFF), which is essential for the survival and development of B cells, is mainly produced by myeloid cells such as macrophages. Abnormal macrophage infiltration and high BAFF expression in kidney allografts are associated with the occurrence and development of antibody-mediated rejection (ABMR). Nuclear hormone receptor Liver X receptors (LXRs), is a nonnegligible participant in regulating cholesterol metabolism and inflammatory responses. Nowadays the effects of LXRα activation on macrophages have been widely studied, however the effects of LXRα activation on BAFF expression and cell function due to the change of BAFF signaling have not yet been fully investigated. In the present study, LXRα activation alone was found to downregulate BAFF expression in quiescent RAW 264.7 cells, whereas LXRα agonist significantly upregulated BAFF expression in cells pretreated with lipopolysaccharide (LPS) for 6 h. The increased BAFF signaling promoted M1 polarization and enhanced cell viability, migration, and phagocytic ability. LXRα can directly bind to the BAFF promoter region and decrease BAFF expression in RAW264.7 cells. LXRα activation enhanced mitochondrial metabolism, which promoted BAFF expression in the LPS-activated cells. Our results indicate that subtle changes in the microenvironment would affect the biological function of macrophages, in which a variety of BAFF signaling pathways may also be involved, providing a new perspective on exploring the mechanism of allograft rejection and uncovering the potential reason for the unstable efficacy of anti-BAFF preparations in kidney transplant recipients.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151067"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779363","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
Structural analysis of ExaC, an NAD+-dependent aldehyde dehydrogenase, from Pseudomonas aeruginosa.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1016/j.bbrc.2024.151077
Ji Hyuk Ko, Kang Hwa Jeong, Su Bin Son, Jae Young Lee
{"title":"Structural analysis of ExaC, an NAD<sup>+</sup>-dependent aldehyde dehydrogenase, from Pseudomonas aeruginosa.","authors":"Ji Hyuk Ko, Kang Hwa Jeong, Su Bin Son, Jae Young Lee","doi":"10.1016/j.bbrc.2024.151077","DOIUrl":"10.1016/j.bbrc.2024.151077","url":null,"abstract":"<p><p>The opportunistic pathogen Pseudomonas aeruginosa (Pa) utilizes ethanol as an energy source, however, ethanol metabolism generates acetaldehyde, a toxic byproduct. To mitigate this toxicity, P. aeruginosa employs aldehyde dehydrogenases (ALDHs) to oxidize acetaldehyde into less harmful compounds. ExaC, an NAD<sup>+</sup>-dependent ALDH from P. aeruginosa (PaExaC) and a member of group X ALDHs, plays a critical role in this detoxification by oxidizing both aldehydes and hydrazones. In this study, we determined the crystal structures of PaExaC in its apo and NAD<sup>+</sup> -bound forms. PaExaC functions as a homodimer, with three distinct domains: an NAD<sup>+</sup> binding domain, a catalytic domain, and an oligomerization domain. Structural analyses revealed that PaExaC's substrate entry channel (SEC) is optimized for size-selective aldehyde metabolism, with Leu120, Tyr462, and Thr302. Comparative structural and docking analyses with other ALDHs further validated PaExaC's preference for small aliphatic aldehydes and hydrazones. These findings highlight PaExaC's role in aldehyde detoxification, facilitating P. aeruginosa survival in diverse environments, and provide structural insights for developing targeted inhibitors to help treat infections.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151077"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790946","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
PIEZO1-mediated calcium influx transiently alters nuclear mechanical properties via actin remodeling in chondrocytes.
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.2024.151135
Jaquelin M Garcia-Castorena, Rosa Riester, Miranda Gamino-Ornelas, Nikitha Ada, Farshid Guilak, Marina Danalache
{"title":"PIEZO1-mediated calcium influx transiently alters nuclear mechanical properties via actin remodeling in chondrocytes.","authors":"Jaquelin M Garcia-Castorena, Rosa Riester, Miranda Gamino-Ornelas, Nikitha Ada, Farshid Guilak, Marina Danalache","doi":"10.1016/j.bbrc.2024.151135","DOIUrl":"10.1016/j.bbrc.2024.151135","url":null,"abstract":"<p><p>Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca<sup>2+</sup> ion channel, has been shown to be important in sensing mechanical stress, however its signal transduction pathway is not thoroughly understood. In this study, we used primary porcine chondrocytes to determine whether PIEZO1 activation and subsequent Ca<sup>2+</sup> influx altered nuclear mechanical properties, and whether these effects involved the actin cytoskeleton. We discovered that activating PIEZO1 with Yoda1, a specific small-molecule agonist, induces transient nuclear softening-a previously identified mechanoprotective response. This PIEZO1-mediated nuclear softening is abolished by inhibiting actin cytoskeleton remodeling with Latrunculin A or by removing extracellular Ca<sup>2+</sup>. Notably, PIEZO1-mediated nuclear softening did not lead to significant changes in gene expression or heterochromatin methylation. Our findings demonstrate that actin cytoskeleton remodeling following Ca<sup>2+</sup> influx facilitates PIEZO1 signal transduction to the nucleus but does not induce lasting gene expression changes.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151135"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817099","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
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