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Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice. 膳食丙酮酸以细胞膜磷脂酶 A2 为靶标,减轻小鼠的炎症和肥胖。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwae014
Sadaf Hasan, Nabil Ghani, Xiangli Zhao, Julia Good, Amanda Huang, Hailey Lynn Wrona, Jody Liu, Chuan-Ju Liu
{"title":"Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice.","authors":"Sadaf Hasan, Nabil Ghani, Xiangli Zhao, Julia Good, Amanda Huang, Hailey Lynn Wrona, Jody Liu, Chuan-Ju Liu","doi":"10.1093/procel/pwae014","DOIUrl":"10.1093/procel/pwae014","url":null,"abstract":"<p><p>Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation, known as meta-inflammation. This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease. Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways. However, its role and molecular mechanism in obesity and associated complications are obscure. In this study, we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain, white adipose tissue inflammation, and metabolic dysregulation. To identify the target proteins of pyruvate, drug affinity responsive target stability was employed with proteomics, cellular thermal shift assay, and isothermal drug response to detect the interactions between pyruvate and its molecular targets. Consequently, we identified cytosolic phospholipase A2 (cPLA2) as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity, white adipose tissue inflammation, and hepatic steatosis in a cPLA2-dependent manner. Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated, confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity. Overall, our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its action. Pyruvate's prior clinical use indicates that it can be considered a safe and viable alternative for obesity, whether consumed as a dietary supplement or as part of a regular diet.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"661-685"},"PeriodicalIF":13.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis. 铁蛋白沉积途径的蛋白质组分析揭示了 CEPT1 在抑制铁蛋白沉积中的作用。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwae004
Xiaoguang Liu, Zhen Chen, Yuelong Yan, Fereshteh Zandkarimi, Litong Nie, Qidong Li, Amber Horbath, Kellen Olszewski, Lavanya Kondiparthi, Chao Mao, Hyemin Lee, Li Zhuang, Masha Poyurovsky, Brent R Stockwell, Junjie Chen, Boyi Gan
{"title":"Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis.","authors":"Xiaoguang Liu, Zhen Chen, Yuelong Yan, Fereshteh Zandkarimi, Litong Nie, Qidong Li, Amber Horbath, Kellen Olszewski, Lavanya Kondiparthi, Chao Mao, Hyemin Lee, Li Zhuang, Masha Poyurovsky, Brent R Stockwell, Junjie Chen, Boyi Gan","doi":"10.1093/procel/pwae004","DOIUrl":"10.1093/procel/pwae004","url":null,"abstract":"<p><p>Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"686-703"},"PeriodicalIF":13.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The expanded application of CAR-T cell therapy for the treatment of multiple non-tumoral diseases. 扩大 CAR-T 细胞疗法在治疗多种非肿瘤性疾病方面的应用。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwad061
Zhuoqun Liu, Yuchen Xiao, Jianjun Lyu, Duohui Jing, Liu Liu, Yanbin Fu, Wenxin Niu, Lingjing Jin, Chao Zhang
{"title":"The expanded application of CAR-T cell therapy for the treatment of multiple non-tumoral diseases.","authors":"Zhuoqun Liu, Yuchen Xiao, Jianjun Lyu, Duohui Jing, Liu Liu, Yanbin Fu, Wenxin Niu, Lingjing Jin, Chao Zhang","doi":"10.1093/procel/pwad061","DOIUrl":"10.1093/procel/pwad061","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"633-641"},"PeriodicalIF":13.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond. 癌症中的代谢性细胞死亡:铁蜕变、杯蜕变、二硫化碳蜕变及其他。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwae003
Chao Mao, Min Wang, Li Zhuang, Boyi Gan
{"title":"Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond.","authors":"Chao Mao, Min Wang, Li Zhuang, Boyi Gan","doi":"10.1093/procel/pwae003","DOIUrl":"10.1093/procel/pwae003","url":null,"abstract":"<p><p>Cell death resistance represents a hallmark of cancer. Recent studies have identified metabolic cell death as unique forms of regulated cell death resulting from an imbalance in the cellular metabolism. This review discusses the mechanisms of metabolic cell death-ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, and alkaliptosis-and explores their potential in cancer therapy. Our review underscores the complexity of the metabolic cell death pathways and offers insights into innovative therapeutic avenues for cancer treatment.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"642-660"},"PeriodicalIF":13.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia. 巨噬细胞通过 NLRP3 信号通路分泌的 Lcn2 可诱发重症肺炎。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-24 DOI: 10.1093/procel/pwae045
Mingya Liu, Feifei Qi, Jue Wang, Fengdi Li, Qi Lv, Ran Deng, Xujian Liang, Shasha Zhou, Pin Yu, Yanfeng Xu, Yaqing Zhang, Yiwei Yan, Ming Liu, Shuyue Li, Guocui Mou, Linlin Bao
{"title":"Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia.","authors":"Mingya Liu, Feifei Qi, Jue Wang, Fengdi Li, Qi Lv, Ran Deng, Xujian Liang, Shasha Zhou, Pin Yu, Yanfeng Xu, Yaqing Zhang, Yiwei Yan, Ming Liu, Shuyue Li, Guocui Mou, Linlin Bao","doi":"10.1093/procel/pwae045","DOIUrl":"https://doi.org/10.1093/procel/pwae045","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Molecular architecture of mammalian pyruvate dehydrogenase complex. 哺乳动物丙酮酸脱氢酶复合物的分子结构。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-24 DOI: 10.1093/procel/pwae044
Maofei Chen, Yutong Song, Sensen Zhang, Yitang Zhang, Xudong Chen, Minghui Zhang, Meng Han, Xin Gao, Sai Li, Maojun Yang
{"title":"Molecular architecture of mammalian pyruvate dehydrogenase complex.","authors":"Maofei Chen, Yutong Song, Sensen Zhang, Yitang Zhang, Xudong Chen, Minghui Zhang, Meng Han, Xin Gao, Sai Li, Maojun Yang","doi":"10.1093/procel/pwae044","DOIUrl":"https://doi.org/10.1093/procel/pwae044","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Adenosine-to-Inosine RNA editing in cancer: molecular mechanisms and downstream targets. 癌症中的腺苷转肌苷 RNA 编辑:分子机制和下游靶点。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-10 DOI: 10.1093/procel/pwae039
Hao Cheng, Jun Yu, Chi Chun Wong
{"title":"Adenosine-to-Inosine RNA editing in cancer: molecular mechanisms and downstream targets.","authors":"Hao Cheng, Jun Yu, Chi Chun Wong","doi":"10.1093/procel/pwae039","DOIUrl":"10.1093/procel/pwae039","url":null,"abstract":"<p><p>Adenosine-to-Inosine (A-to-I), one of the most prevalent RNA modifications, has recently garnered significant attention. The A-to-I modification actively contributes to biological and pathological processes by affecting the structure and function of various RNA molecules, including double stranded RNA, transfer RNA, microRNA, and viral RNA. Increasing evidence suggests that A-to-I plays a crucial role in the development of human disease, particularly in cancer, and aberrant A-to-I levels are closely associated with tumorigenesis and progression through regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of A-to-I modification in cancer are not comprehensively understood. Here, we review the latest advances regarding the A-to-I editing pathways implicated in cancer, describing their biological functions and their connections to the disease.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Advances in Gene and Cellular Therapeutic Approaches for Huntington's Disease. 亨廷顿氏症基因和细胞治疗方法的进展。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-09 DOI: 10.1093/procel/pwae042
Xuejiao Piao, Dan Li, Hui Liu, Qing Guo, Yang Yu
{"title":"Advances in Gene and Cellular Therapeutic Approaches for Huntington's Disease.","authors":"Xuejiao Piao, Dan Li, Hui Liu, Qing Guo, Yang Yu","doi":"10.1093/procel/pwae042","DOIUrl":"https://doi.org/10.1093/procel/pwae042","url":null,"abstract":"<p><p>Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and non-pharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Correction to: Macrophages suppress cardiac reprogramming of fibroblasts in vivo via IFN-mediated intercellular self-stimulating circuit. 更正为巨噬细胞通过 IFN 介导的细胞间自我刺激回路抑制体内成纤维细胞的心脏重编程。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-07 DOI: 10.1093/procel/pwae038
{"title":"Correction to: Macrophages suppress cardiac reprogramming of fibroblasts in vivo via IFN-mediated intercellular self-stimulating circuit.","authors":"","doi":"10.1093/procel/pwae038","DOIUrl":"https://doi.org/10.1093/procel/pwae038","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens. 磷脂酰肌醇-4,5-二磷酸的内分解代谢是建立抵御病原体能力的基础。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-01 DOI: 10.1093/procel/pwae041
Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi
{"title":"Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.","authors":"Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi","doi":"10.1093/procel/pwae041","DOIUrl":"https://doi.org/10.1093/procel/pwae041","url":null,"abstract":"<p><p>Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of C. elegans with P. aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal PI(4,5)P2 and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity, and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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