Apoptosis最新文献_第9页

Retraction Note: The analog of cGAMP, c-di-AMP, activates STING mediated cell death pathway in estrogen-receptor negative breast cancer cells 注：cGAMP的类似物c-di-AMP在雌激素受体阴性的乳腺癌细胞中激活STING介导的细胞死亡途径。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-04-07 DOI: 10.1007/s10495-025-02110-3

Hitesh Vasiyani, Anjali Shinde, Milton Roy, Minal Mane, Kritarth Singh, Jyoti Singh, Dhruv Gohel, Fatema Currim, Khushali Vaidya, Mahesh Chhabria, Rajesh Singh

引用次数: 0

Correction: Atorvastatin inhibits the apoptosis of human umbilical vein endothelial cells induced by angiotensin II via the lysosomalmitochondrial axis 更正：阿托伐他汀通过溶酶体线粒体轴抑制血管紧张素II诱导的人脐静脉内皮细胞凋亡。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-04-07 DOI: 10.1007/s10495-025-02100-5

Ye Chang, Yuan Li, Ning Ye, Xiaofan Guo, Zhao Li, Guozhe Sun, Yingxian Sun

引用次数: 0

Bufalin inhibits immune escape in metastatic colorectal cancer by regulating M2 macrophage polarization 布法林通过调节M2巨噬细胞极化抑制转移性结直肠癌的免疫逃逸

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-04-05 DOI: 10.1007/s10495-025-02107-y

Chang Lu, Jing Shang, Manli Xie, Yuan Zhu, Jiani Zhong, Yujie He, Zengyou Xiao, Wen Chen, Ze-An Yang, Xiaoxia Tang, Peihao Yin, Jinbao Chen

{"title":"Bufalin inhibits immune escape in metastatic colorectal cancer by regulating M2 macrophage polarization","authors":"Chang Lu, Jing Shang, Manli Xie, Yuan Zhu, Jiani Zhong, Yujie He, Zengyou Xiao, Wen Chen, Ze-An Yang, Xiaoxia Tang, Peihao Yin, Jinbao Chen","doi":"10.1007/s10495-025-02107-y","DOIUrl":"10.1007/s10495-025-02107-y","url":null,"abstract":"<div><p>The prognosis for patients with metastatic colorectal cancer (mCRC) remains poor primarily owing to immune escape caused by immunosuppressive tumor microenvironment (TME). M2 tumor-associated macrophages (TAMs) have been considered as a pivotal role in sustaining the immunosuppressive character in TME. Our previous studies have found that highly mCRC cells could promote M2 TAMs polarization, leading to the exhaustion of T cell antitumor immunity. Studies have reported that Bufalin (BU) could reverse the immunosuppressive TME via regulating TAMs polarization, but the mechanisms underlying remain elusive. In this study, we demonstrated that KLF4 secreted by highly mCRC cells not only promoted the polarization to M2 TAMs but also up-regulated the PD-L1 expression in TAMs, leading to suppressing cytotoxic T lymphocyte (CTL) function to facilitate tumor immune escape. Mechanistically, BU targeted the SRC-3 protein to reduce KLF4 release in highly mCRC cells to regulate the polarization of M2 TAMs and down-regulate PD-L1 expression in TAMs, resulting in reprogramming of the TME and enhancing the anti-tumor immunity. These results have also been validated in both subcutaneous tumor models and orthotopic tumor models. Overall, this research further elucidates the anti-tumor mechanism of BU for inhibiting immune escape in mCRC and facilitate exploitation of a new potential macrophage-based mCRC immunotherapeutic modality.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 5-6","pages":"1467 - 1481"},"PeriodicalIF":8.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Ochratoxin A-induced mitochondrial pathway apoptosis and ferroptosis by promoting glycolysis 赭曲霉毒素a通过促进糖酵解诱导线粒体通路凋亡和铁下垂。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-04-01 DOI: 10.1007/s10495-025-02109-w

Yao Zhou, Wenying Chen, Shiyu Feng, Shuangchao Liu, Cheng Chen, Bingxu Yao, Xiao Li Shen

{"title":"Ochratoxin A-induced mitochondrial pathway apoptosis and ferroptosis by promoting glycolysis","authors":"Yao Zhou, Wenying Chen, Shiyu Feng, Shuangchao Liu, Cheng Chen, Bingxu Yao, Xiao Li Shen","doi":"10.1007/s10495-025-02109-w","DOIUrl":"10.1007/s10495-025-02109-w","url":null,"abstract":"<div><p>Ochratoxin A (OTA), a toxic secondary metabolite recognized for its harmful effects on the kidneys, and it is commonly present in various foods and animal feeds. Although there have been few reports on the involvement of metabolic enzymes in OTA-induced nephrotoxicity and metabolic reprogramming in OTA-induced digestive tract toxicity, it remains unclear whether OTA’s primary nephrotoxic effects are mediated through metabolic reprogramming. In this study, we examined the effects of OTA and/or 2-deoxy-D-glucose (2-DG) on cell viability, levels of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and lactic acid (LA), as well as protein levels in human proximal tubule epithelial (HK-2) cells. The results indicate that OTA leads to a reduction in GSH levels and the protein levels of Lon protease 1 (Lonp1), tumor necrosis factor receptor-associated protein 1 (TRAP1), mitochondrial pyruvate carrier 1 (MPC1), glutathione peroxidase 4 (GPX4), B-cell lymphoma-2 (Bcl-2), and Bcl-2-like protein 1 (Bcl-xl), while increasing ROS, MDA, and LA levels, as well as the protein levels of glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), pyruvate kinase 2 (PKM2), ATP-dependent 6-phosphofructokinase, platelet type (PFKP), long-chain fatty acid-CoA ligase 4 (ACSL4), Bcl-2-associated X protein (Bax), and cyclophilin D (CYPD) (<i>P</i> < 0.05). In conclusion, OTA induces mitochondrial pathway apoptosis and ferroptosis by disturbing mitochondrial homeostasis via the inhibition of Lonp1 and TRAP1, thereby reducing GSH levels, increasing ROS, MDA, and LA levels, and promoting glycolysis in vitro. This is the first report on OTA-induced mitochondrial pathway apoptosis and ferroptosis facilitated by mitochondrial homeostasis imbalance-mediated glycolysis in HK-2 cells.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 5-6","pages":"1440 - 1452"},"PeriodicalIF":8.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 impact of YTHDF2-mediated NCOA4 methylation on myocardial ferroptosis ythdf2介导的NCOA4甲基化对心肌铁下垂的影响。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-04-01 DOI: 10.1007/s10495-025-02106-z

Xiaoqi Shao, Mengxian Sun, Ruonan Wang, Mingyang Leng, Hongtao Diao, Xu Li, Dongwei Wang, Kaili Wu, Liang Wang, Wen Lv, Xianglu Rong, Yue Zhang

{"title":"The impact of YTHDF2-mediated NCOA4 methylation on myocardial ferroptosis","authors":"Xiaoqi Shao, Mengxian Sun, Ruonan Wang, Mingyang Leng, Hongtao Diao, Xu Li, Dongwei Wang, Kaili Wu, Liang Wang, Wen Lv, Xianglu Rong, Yue Zhang","doi":"10.1007/s10495-025-02106-z","DOIUrl":"10.1007/s10495-025-02106-z","url":null,"abstract":"<div><p>The N6-Methyladenosine (m6A) modification is prevalent across various RNA species, including messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs), and has garnered significant interest due to its potential implications in cardiovascular disease. Despite extensive research, the precise relationship between m6A and myocardial infarction (MI) remains inadequately understood. The human YTH domain family 2 (YTHDF2) protein has emerged as a critical factor in this context, selectively recognizing m6A-modified RNAs and modulating their degradation. Our investigation revealed that the knockdown of YTHDF2 markedly enhanced ferroptosis in vitro, whereas the overexpression of YTHDF2 exhibited a significant protective effect. Mechanistically, it was elucidated that YTHDF2 suppresses the expression of nuclear receptor coactivator 4 (NCOA4) via m6A methylation. Furthermore, the inhibition of cardiomyocyte ferroptosis by YTHDF2 is contingent upon its regulation of NCOA4. Additionally, the enzyme methyltransferase-like 3 (METTL3) was identified as a pivotal factor in the m6A-mediated degradation of NCOA4 mRNA. Taken together, our results highlight the significant role of YTHDF2-mediated NCOA4 m6A methylation in the regulation of myocardial infarction and myocardial ferroptosis, suggesting that YTHDF2 may be a promising target for therapeutic interventions in myocardial infarction.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 5-6","pages":"1453 - 1466"},"PeriodicalIF":8.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development X-linked inhibitor of apoptosis protein （XIAP）在肿瘤发生中的关键作用。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-03-27 DOI: 10.1007/s10495-025-02101-4

Hui Fan, Jiyuan Liu, Xiangyan Hu, Jiye Cai, Bo Su, Jinhuan Jiang

引用次数: 0

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-03-27 DOI: 10.1007/s10495-025-02103-2

Wanjin Chen, Kailin Liu, Zhiling Wang, Hui Zhang, Ming Tan, Yuting Liu, Tingting Gao, Xiameng Su, Leirong Gu, Xinyan Chen, Shengtao Cheng

{"title":"Migrasome-related ITGA5 for predicting prognosis, immune infiltration and drug sensitivity of hepatocellular carcinoma","authors":"Wanjin Chen, Kailin Liu, Zhiling Wang, Hui Zhang, Ming Tan, Yuting Liu, Tingting Gao, Xiameng Su, Leirong Gu, Xinyan Chen, Shengtao Cheng","doi":"10.1007/s10495-025-02103-2","DOIUrl":"10.1007/s10495-025-02103-2","url":null,"abstract":"<div><p>To clarify the biological functions and prognostic significance of migrasome-related integrin subunit alpha 5 (ITGA5) in hepatocellular carcinoma (HCC). We used The Cancer Genome Atlas datasets and RNA-seq data from nine sets of paired HCC and adjacent normal tissues to identify key migrasome-related genes through a comprehensive analysis and weighted correlation network analysis. We then confirmed their roles in HCC through analyses of gene mutations, methylation, and immune cell infiltration, as well as molecular docking, molecular dynamics, and cell experiments. A comprehensive analysis of migrasome-related genes showed that ITGA5 was a critical gene related to HCC, and it is highly expressed in HCC tissues, which is related to poor prognosis. Further enrichment analysis revealed that ITGA5 is involved in many pathways related to tumor occurrence and metastasis, such as the PI3K–AKT pathway. In addition, ITGA5 was found to be expressed in multiple types of immune cells and was closely associated with immune infiltration. Drug sensitivity, molecular docking, and molecular dynamics analyses indicated that ITGA5 may enhance the sensitivity of HCC to drug TGX221. Finally, cell phenotype experiments confirmed that ITGA5 knockdown suppressed the proliferation, migration, and invasion of HCC cells, and while overexpression exacerbated malignant phenotypes. Our analyses showed that ITGA5 is a key migrasome-related gene involved in the proliferation and metastasis of HCC that has promise as a therapeutic target and candidate prognostic indicator.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 5-6","pages":"1424 - 1439"},"PeriodicalIF":8.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Necroptosis in myocardial ischaemia-reperfusion injury: current update on mechanisms, therapeutic targets, and translational potential 心肌缺血-再灌注损伤中的坏死性下垂：机制、治疗靶点和转化潜力的最新进展。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-03-27 DOI: 10.1007/s10495-025-02108-x

Siarhei A. Dabravolski, Vladislav A. Kalmykov, Anastasia O. Maksaeva, Ulyana V. Rozhkova, Ksenia O. Lapshina, Alexander N. Orekhov

{"title":"Necroptosis in myocardial ischaemia-reperfusion injury: current update on mechanisms, therapeutic targets, and translational potential","authors":"Siarhei A. Dabravolski, Vladislav A. Kalmykov, Anastasia O. Maksaeva, Ulyana V. Rozhkova, Ksenia O. Lapshina, Alexander N. Orekhov","doi":"10.1007/s10495-025-02108-x","DOIUrl":"10.1007/s10495-025-02108-x","url":null,"abstract":"<div><p>Necroptosis is a programmed form of cell death that has gained significant attention in the field of cardiovascular research due to its involvement in myocardial infarction (MI) and myocardial ischaemia-reperfusion (I/R) injury. Unlike apoptosis, necroptosis elicits a pro-inflammatory response, contributing to myocardial injury, fibrosis, and adverse remodelling. This review aims to provide an overview of the molecular mechanisms underlying necroptosis, with a particular focus on its role in myocardial I/R injury. Key regulatory proteins such as Receptor-interacting protein kinase 3 (RIPK3) and Mixed lineage kinase domain-like protein (MLKL) are central to the necroptotic process, mediating cell death and inflammation. The review discusses the potential of targeting necroptosis as a therapeutic strategy for managing cardiovascular diseases, particularly post-MI. The RIPK3-CaMKII-mitochondrial permeability transition pore (mPTP) pathway is identified as a critical signalling axis in necroptosis and its inhibition may offer protective benefits in myocardial injury. The review also considers the role of natural and chemical inhibitors and other genes in necroptosis regulation. Overall, targeting necroptosis represents a promising avenue for therapeutic intervention to mitigate cardiac injury, promote recovery, and improve long-term patient outcomes in cardiovascular diseases.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 5-6","pages":"1216 - 1234"},"PeriodicalIF":8.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pharmacological inhibition of STING-mediated GPX4 autophagic degradation by 4-octyl itaconate ameliorates sepsis-induced acute kidney injury 4-辛酯衣康酸对sting介导的GPX4自噬降解的药理抑制可改善脓毒症诱导的急性肾损伤。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-03-22 DOI: 10.1007/s10495-025-02099-9

Yiyang Wang, Miao Zhou, Ruo-yu Jiang, Cheng-long Zhu

{"title":"Pharmacological inhibition of STING-mediated GPX4 autophagic degradation by 4-octyl itaconate ameliorates sepsis-induced acute kidney injury","authors":"Yiyang Wang, Miao Zhou, Ruo-yu Jiang, Cheng-long Zhu","doi":"10.1007/s10495-025-02099-9","DOIUrl":"10.1007/s10495-025-02099-9","url":null,"abstract":"<div><p>The precise pathogenic mechanisms underlying sepsis-induced acute kidney injury (AKI) remain elusive. Emerging evidence suggests a link between tubular ferroptosis and the pathogenesis of AKI, though the regulatory pathways are not fully understood. Stimulator of interferon genes (STING), previously recognized as a pivotal mediator of innate immunity via DNA-sensing pathways, is increasingly associated with lipid peroxidation, a hallmark of ferroptosis, and 4-octyl itaconate (4-OI) has been shown to inhibit STING activation, exerting anti-inflammatory effects. This study investigates the protective mechanisms of 4-OI in sepsis-AKI. Following cecal ligation and puncture (CLP), inflammation, oxidative stress, and ferroptosis levels in kidney tissue increased. Both 4-OI and ferrostatin-1 (Fer-1) mitigated renal ferroptosis, exerting anti-inflammatory and antioxidant stress effects, and improved renal function. Consistently, in vitro experiments demonstrated that 4-OI reduced ferroptosis in human renal proximal tubule (HK-2) cells induced by lipopolysaccharide (LPS). Mechanistically, 4-OI suppressed LPS-induced activation of the STING pathway and reduced levels of inflammatory cytokines in a manner independent of NF-E2-related factor 2 (Nrf2). Additionally, 4-OI inhibited STING transcription through the activation of Nrf2. These dual actions effectively suppressed LPS-induced STING pathway activation, thereby inhibiting STING-mediated autophagic degradation of glutathione peroxidase 4 (GPX4), reducing reactive oxygen species (ROS) accumulation, and alleviating ferroptosis. In summary, 4-OI is a promising therapeutic candidate, functioning both as a STING inhibitor and a ferroptosis inhibitor, with potential applications in the treatment of sepsis.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 5-6","pages":"1410 - 1423"},"PeriodicalIF":8.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Activation of the 20S proteasome core particle prevents cell death induced by oxygen- and glucose deprivation in cultured cortical neurons 20S蛋白酶体核心颗粒的激活可防止培养皮层神经元缺氧和葡萄糖剥夺引起的细胞死亡。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-03-17 DOI: 10.1007/s10495-025-02097-x

Ivan L. Salazar, Michele Curcio, Miranda Mele, Rossela Vetrone, Simone Frisari, Rui O. Costa, Margarida V. Caldeira, Darci J. Trader, Carlos B. Duarte

{"title":"Activation of the 20S proteasome core particle prevents cell death induced by oxygen- and glucose deprivation in cultured cortical neurons","authors":"Ivan L. Salazar, Michele Curcio, Miranda Mele, Rossela Vetrone, Simone Frisari, Rui O. Costa, Margarida V. Caldeira, Darci J. Trader, Carlos B. Duarte","doi":"10.1007/s10495-025-02097-x","DOIUrl":"10.1007/s10495-025-02097-x","url":null,"abstract":"<div><p>Neuronal damage in brain ischemia is characterized by a disassembly of the proteasome and a decrease in its proteolytic activity. However, to what extent these alterations are coupled to neuronal death is controversial since proteasome inhibitors were shown to provide protection in different models of stroke in rodents. This question was addressed in the present work using cultured rat cerebrocortical neurons subjected to transient oxygen- and glucose-deprivation (OGD) as a model for in vitro ischemia. Under the latter conditions there was a time-dependent loss in the proteasome activity, determined by cleavage of the Suc-LLVY-AMC fluorogenic substrate, and the disassembly of the proteasome, as assessed by native-polyacrylamide gel electrophoresis followed by western blot against Psma2 and Rpt6, which are components of the catalytic core and regulatory particle, respectively. Immunocytochemistry experiments against the two proteins also showed differential effects on their dendritic distribution. OGD also downregulated the protein levels of Rpt3 and Rpt10, two components of the regulatory particle, by a mechanism dependent on the activity of NMDA receptors and mediated by calpains. Activation of the proteasome activity, using an inhibitor of USP14, a deubiquitinase enzyme, inhibited OGD-induced cell death, and decreased calpain activity as determined by analysis of spectrin cleavage. Similar results were obtained in the presence of two oleic amide derivatives (B12 and D3) which directly activate the 20S proteasome core particle. Together, these results show that proteasome activation prevents neuronal death in cortical neurons subjected to in vitro ischemia, indicating that inhibition of the proteasome is a mediator of neuronal death in brain ischemia.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 5-6","pages":"1372 - 1390"},"PeriodicalIF":8.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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