Cell Death Discovery最新文献

Correction: The possible involvement of circRNA DMNT1/p53/JAK/STAT in gestational diabetes mellitus and preeclampsia. 更正：circRNA DMNT1/p53/JAK/STAT 可能与妊娠糖尿病和子痫前期有关。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-04 DOI: 10.1038/s41420-024-02065-5

Dongqin Bao, Chaohui Zhuang, Yan Jiao, Li Yang

引用次数: 0

Overexpressed nicotinamide N‑methyltransferase in endometrial stromal cells induced by macrophages and estradiol contributes to cell proliferation in endometriosis. 在巨噬细胞和雌二醇的诱导下，子宫内膜基质细胞中烟酰胺 N-甲基转移酶过度表达，导致子宫内膜异位症细胞增殖。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-03 DOI: 10.1038/s41420-024-02229-3

Shuhui Hou, Hui Xu, Shating Lei, Dong Zhao

{"title":"Overexpressed nicotinamide N‑methyltransferase in endometrial stromal cells induced by macrophages and estradiol contributes to cell proliferation in endometriosis.","authors":"Shuhui Hou, Hui Xu, Shating Lei, Dong Zhao","doi":"10.1038/s41420-024-02229-3","DOIUrl":"10.1038/s41420-024-02229-3","url":null,"abstract":"Endometriosis, an estrogen-dependent chronic inflammatory condition, afflicts reproductive-aged women. However, the underlying pathological mechanisms remain to be elucidated. Nicotinamide N-methyltransferase (NNMT) is a critical enzyme involved in cellular metabolism and methylation regulation. This study investigated the role of NNMT in endometriosis. By analyzing datasets GSE5108, GSE7305, GSE141549, GSE23339, and GSE25628, we identified a significant overexpression of NNMT in the eutopic endometrium and ectopic lesions of endometriosis patients compared to normal endometrium. Furthermore, NNMT was upregulated in collected endometrioma specimens and isolated primary endometrial stromal cells (ESCs) compared to their respective controls. Inhibition of NNMT using JBSNF-000088 attenuated the proliferation, migration, and invasion of ESCs. In vivo, treatment of mouse models of endometriosis with JBSNF-000088 resulted in a marked reduction in lesion weight and quantity. NNMT expression in ESCs was dose-dependently upregulated by 17β-estradiol at concentrations of 1 nM, 10 nM, and 100 nM, an effect that was attenuated by 10 nM progesterone. Additionally, treating HESCs with macrophage-conditioned medium elevated NNMT expression at both mRNA and protein levels. Knockdown of NNMT impeded the proliferation, migration, and invasion of ESCs, which was paralleled by decreased phosphorylation levels of Erb-b2 receptor tyrosine kinase 4 (ERBB4), PI3K, and AKT. Conversely, overexpressing ERBB4 mitigated the NNMT knockdown-induced decline in phosphorylated PI3K and AKT and rescued the proliferation of ESCs. Altogether, these results indicate that the overexpression of NNMT induced by estrogen and macrophage interaction modulates ESC proliferation via the NNMT-ERBB4-PI3K/AKT signaling pathway, as well as promotes cellular migration and invasion, contributing to the development of endometriosis.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567418","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

Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells. 靶向 HECTD3-p62 轴可提高三阴性乳腺癌细胞的放射敏感性。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-01 DOI: 10.1038/s41420-024-02154-5

Maobo Huang, Wenjing Liu, Zhuo Cheng, Fubing Li, Yanjie Kong, Chuanyu Yang, Yu Tang, Dewei Jiang, Wenhui Li, Yudie Hu, Jinhui Hu, PemaTenzin Puno, Ceshi Chen

引用次数: 0

Lipids associated with autophagy: mechanisms and therapeutic targets. 与自噬有关的脂质：机制和治疗目标。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-30 DOI: 10.1038/s41420-024-02224-8

Michał Jarocki, Kacper Turek, Jolanta Saczko, Mounir Tarek, Julita Kulbacka

{"title":"Lipids associated with autophagy: mechanisms and therapeutic targets.","authors":"Michał Jarocki, Kacper Turek, Jolanta Saczko, Mounir Tarek, Julita Kulbacka","doi":"10.1038/s41420-024-02224-8","DOIUrl":"10.1038/s41420-024-02224-8","url":null,"abstract":"Autophagy is a molecular process essential for maintaining cellular homeostasis, with its impairment or dysregulation linked to the progression of various diseases in mammals. Specific lipids, including phosphoinositides, sphingolipids, and oxysterols, play pivotal roles in inducing and regulating autophagy, highlighting their significance in this intricate process. This review focuses on the critical involvement of these lipids in autophagy and lipophagy, providing a comprehensive overview of the current understanding of their functions. Moreover, we delve into how abnormalities in autophagy, influenced by these lipids, contribute to the pathogenesis of various diseases. These include age-related conditions such as cardiovascular diseases, neurodegenerative disorders, type 2 diabetes, and certain cancers, as well as inflammatory and liver diseases, skeletal muscle pathologies and age-related macular degeneration (AMD). This review aims to highlight function of lipids and their potential as therapeutic targets in treating diverse human pathologies by elucidating the specific roles of phosphoinositides, sphingolipids, and oxysterols in autophagy.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544030","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

Myocardial ischemia-reperfusion injury upregulates nucleostemin expression via HIF-1α and c-Jun pathways and alleviates apoptosis by promoting autophagy. 心肌缺血再灌注损伤可通过 HIF-1α 和 c-Jun 通路上调 nucleostemin 的表达，并通过促进自噬缓解细胞凋亡。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-30 DOI: 10.1038/s41420-024-02221-x

Xiao Han, Zhicheng Jiang, Yufeng Hou, Xiaorong Zhou, Baoying Hu

{"title":"Myocardial ischemia-reperfusion injury upregulates nucleostemin expression via HIF-1α and c-Jun pathways and alleviates apoptosis by promoting autophagy.","authors":"Xiao Han, Zhicheng Jiang, Yufeng Hou, Xiaorong Zhou, Baoying Hu","doi":"10.1038/s41420-024-02221-x","DOIUrl":"10.1038/s41420-024-02221-x","url":null,"abstract":"Myocardial ischemia-reperfusion (I/R) injury, often arising from interventional therapy for acute myocardial infarction, leads to irreversible myocardial cell death. While previous studies indicate that nucleostemin (NS) is induced by myocardial I/R injury and mitigates myocardial cell apoptosis, the underlying mechanisms are poorly understood. Here, our study reveals that NS upregulation is critical for preventing cardiomyocyte death following myocardial I/R injury. Elevated NS protein levels were observed in myocardial I/R injury mouse and rat models, as well as Hypoxia/reoxygenation (H/R) cardiac cell lines (H9C2 cells). We identified binding sites for c-Jun and HIF-1α in the NS promoter region. Inhibition of JNK and HIF-1α led to a significant decrease in NS transcription and protein expression. Furthermore, inhibition of autophagy and NS expression promoted myocardial cell apoptosis in H/R. Notably, the cell model showed reduced LC3I transformation to LC3II, downregulated Beclin1, upregulated p62, and altered expression of autophagy-related proteins upon NS interference in H/R cells. These findings suggest that NS expression, driven by c-Jun and HIF-1α pathways, facilitates autophagy, providing protection against both myocardial I/R injury and H/R-induced cardiomyocyte apoptosis.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544032","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

Mitophagy: insights into its signaling molecules, biological functions, and therapeutic potential in breast cancer. 有丝分裂：对其信号分子、生物功能和乳腺癌治疗潜力的深入研究。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-29 DOI: 10.1038/s41420-024-02226-6

Cong Chen, Aizhai Xiang, Xia Lin, Jufeng Guo, Jian Liu, Shufang Hu, Tao Rui, Qianwei Ye

引用次数: 0

Nr1d1 inhibition mitigates intermittent hypoxia-induced pulmonary hypertension via Dusp1-mediated Erk1/2 deactivation and mitochondrial fission attenuation. 抑制 Nr1d1 可通过 Dusp1 介导的 Erk1/2 失活和线粒体裂变衰减缓解间歇性缺氧诱发的肺动脉高压。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-29 DOI: 10.1038/s41420-024-02219-5

Zhou Pan, Yan Yao, Xu Liu, Yixuan Wang, Xinyue Zhang, Shiqian Zha, Ke Hu

{"title":"Nr1d1 inhibition mitigates intermittent hypoxia-induced pulmonary hypertension via Dusp1-mediated Erk1/2 deactivation and mitochondrial fission attenuation.","authors":"Zhou Pan, Yan Yao, Xu Liu, Yixuan Wang, Xinyue Zhang, Shiqian Zha, Ke Hu","doi":"10.1038/s41420-024-02219-5","DOIUrl":"10.1038/s41420-024-02219-5","url":null,"abstract":"Intermittent hypoxia (IH) precipitates pulmonary vasoconstriction, culminating in the onset of pulmonary hypertension (PH) among individuals afflicted with sleep apnea. While Nuclear receptor subfamily 1 group D member 1 (Nr1d1) is progressively recognized as pivotal regulator of cellular physiology, the role in the pathogenesis of IH-induced PH remains largely uncharted. The expression of Nr1d1 was examined in IH-induced rodent PH and in IH-treated PASMCs. To elucidate the contribution of Nr1d1 to the development of IH-induced PH, we employed siRNA to modulate Nr1d1 expression in vitro and employed serotype 1 adeno-associated virus (AAV1) in vivo. Nr1d1 levels were elevated in IH-induced rodents PH lung tissues and IH-treated PASMCs. Knocking down Nr1d1 by AAV1 effectively inhibited PH progression in chronic IH-induced PH models. Mechanistic investigations identified dual specificity phosphatase 1 (Dusp1), as a direct target that Nr1d1 trans-repressed, mediating Nr1d1's regulatory influence on Erk1/2/Drp1 signaling. Nr1d1 deficiency ameliorates mitochondrial dysfunction and fission by restoring Dusp1 dysregulation and Drp1 phosphorylation. Activation of Erk1/2 with PMA reversed the Dusp1-mediated regulation of Drp1 phosphorylation, indicating the involvement of the Erk1/2 pathway in Drp1 phosphorylation controlled by Dusp1. Meanwhile, intermittent hypoxia induced more severe PH in Dusp1 knockout mice compared with wild-type mice. Our data unveil a novel role for Nr1d1 in IH-induced PH pathogenesis and an undisclosed Nr1d1-Dusp1 axis in PASMCs mitochondrial fission regulation.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544033","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

Unraveling the landscape of m6A RNA methylation in wound healing and scars. 揭开伤口愈合和疤痕中 m6A RNA 甲基化的面纱。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-29 DOI: 10.1038/s41420-024-02222-w

Qi Zhang, Liming Dong, Song Gong, Ting Wang

{"title":"Unraveling the landscape of m6A RNA methylation in wound healing and scars.","authors":"Qi Zhang, Liming Dong, Song Gong, Ting Wang","doi":"10.1038/s41420-024-02222-w","DOIUrl":"10.1038/s41420-024-02222-w","url":null,"abstract":"Wound healing is a complex process involving sequential stages of hemostasis, inflammation, proliferation, and remodeling. Multiple cell types and factors, including underlying conditions like diabetes and bacterial colonization, can influence healing outcomes and scar formation. N6-methyladenosine (m6A), a predominant RNA modification, plays crucial roles in gene expression regulation, impacting various biological processes and diseases. m6A regulates embryonic skin morphogenesis, wound repair, and pathophysiological processes like inflammation and angiogenesis. Recent studies have highlighted the role of m6A in wound healing, scar formation, and tissue remodeling. Additionally, m6A presents a unique expression pattern in pathological wounds and scars, potentially influencing wound healing and scar formation through modulating gene expression and cellular signaling, thereby serving as potential biomarkers or therapeutic targets. Targeting m6A modifications are potential strategies to enhance wound healing and reduce scar formation. This review aims to explore the roles and mechanisms of m6A RNA methylation in wound healing and scars, and discuss current challenges and perspectives. Continued research in this field will provide significant value for optimal wound repair and scar treatment.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544035","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

Quantitative chemical proteomics reveals that phenethyl isothiocyanate covalently targets BID to promote apoptosis. 定量化学蛋白质组学揭示了异硫氰酸苯乙酯可共价作用于 BID，从而促进细胞凋亡。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-29 DOI: 10.1038/s41420-024-02225-7

Xiaoshu Dong, Xinqian Yu, Minghao Lu, Yaxin Xu, Liyan Zhou, Tao Peng

{"title":"Quantitative chemical proteomics reveals that phenethyl isothiocyanate covalently targets BID to promote apoptosis.","authors":"Xiaoshu Dong, Xinqian Yu, Minghao Lu, Yaxin Xu, Liyan Zhou, Tao Peng","doi":"10.1038/s41420-024-02225-7","DOIUrl":"10.1038/s41420-024-02225-7","url":null,"abstract":"Naturally occurring isothiocyanates (ITCs) found in cruciferous vegetables, such as benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and sulforaphane (SFN), have attracted significant research interest for their promising anti-cancer activity in vitro and in vivo. While the induction of apoptosis is recognized to play a key role in the anti-cancer effects of ITCs, the specific protein targets and associated upstream events underlying ITC-induced apoptosis remain unknown. In this study, we present a set of chemical probes that are derived from BITC, PEITC, and SFN and equipped with bioorthogonal alkynyl handles to systematically profile the target proteins of ITCs in live cancer cells. Using a competition-based quantitative chemical proteomics approach, we identify a range of candidate target proteins of ITCs enriched in biological processes such as apoptosis. We show that BID, an apoptosis regulator of the Bcl-2 family, is covalently modified by ITCs on its N-terminal cysteines. Functional characterization demonstrates that covalent binding to N-terminal cysteines of BID by PEITC results in conformational changes of the protein and disruption of the self-inhibitory interaction between N- and C-terminal regions of BID, thus unleashing the highly active C-terminal segment to exert downstream pro-apoptotic effects. Consistently, PEITC promotes the cleavage and mitochondrial translocation of BID, leading to a strong induction of apoptosis. We further show that mutation of N-terminal cysteines impairs the N- and C-terminal interaction of BID, relieving the self-inhibition and enhancing its apoptotic activity. Overall, our chemical proteomics profiling and functional studies not only reveal BID as the principal target of PEITC in mediating upstream events for the induction of apoptosis, but also uncover a novel molecular mechanism involving N-terminal cysteines within the first helix of BID in regulating its pro-apoptotic potential.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544034","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

Xanthohumol overcomes osimertinib resistance via governing ubiquitination-modulated Ets-1 turnover. 黄腐醇通过调节泛素化调控的Ets-1周转克服奥希替尼耐药性

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-28 DOI: 10.1038/s41420-024-02220-y

Ying Ma, Ruirui Wang, Jinzhuang Liao, Pengfei Guo, Qiang Wang, Wei Li

{"title":"Xanthohumol overcomes osimertinib resistance via governing ubiquitination-modulated Ets-1 turnover.","authors":"Ying Ma, Ruirui Wang, Jinzhuang Liao, Pengfei Guo, Qiang Wang, Wei Li","doi":"10.1038/s41420-024-02220-y","DOIUrl":"10.1038/s41420-024-02220-y","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is a prevalent and fatal malignancy with a significant global impact. Recent advancements have introduced targeted therapies like tyrosine kinase inhibitors (TKIs) such as osimertinib, which have improved patient outcomes, particularly in those with EGFR mutations. Despite these advancements, acquired resistance to TKIs remains a significant challenge. Hence, one of the current research priorities is understanding the resistance mechanisms and identifying new therapeutic targets to improve therapeutic efficacy. Herein, we identified high expression of c-Met in osimertinib-resistant NSCLC cells, and depletion of c-Met significantly inhibited the proliferation of osimertinib-resistant cells and prolonged survival in mice, suggesting c-Met as an attractive therapeutic target. To identify effective anti-tumor agents targeting c-Met, we screened a compound library containing 641 natural products and found that only xanthohumol exhibited potent inhibitory effects against osimertinib-resistant NSCLC cells. Moreover, combination treatment with xanthohumol and osimertinib sensitized osimertinib-resistant NSCLC cells to osimertinib both in vitro and in vivo. Mechanistically, xanthohumol disrupted the interaction between USP9X and Ets-1, and inhibited the phosphorylation of Ets-1 at Thr38, promoting its degradation, thereby targeting the Ets-1/c-Met signaling axis and inducing intrinsic apoptosis in osimertinib-resistant NSCLC cells. Overall, the research highlights the critical role of targeting c-Met to address osimertinib resistance in NSCLC. By demonstrating the efficacy of xanthohumol in overcoming resistance and enhancing therapeutic outcomes, this study provides valuable insights and potential new strategies for improving the clinical management of NSCLC.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521146","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