{"title":"在 ALI 中，Sec13 通过抑制 Ubqln1 介导的 Pgm1 泛素化促进糖酵解。","authors":"","doi":"10.1016/j.bbadis.2024.167475","DOIUrl":null,"url":null,"abstract":"<div><p>Acute lung injury (ALI) is a severe lung damage characterized by acute hypoxemia, increased pulmonary vascular permeability, and inflammatory reactions. Despite current treatments, mortality from ALI remains high. This study found that Sec13 is highly expressed in ALI and regulates it by glycolysis and epithelial-mesenchymal transition (EMT). In an ALI mouse model and cell model, Sec13 expression increased, accompanied by enhanced glycolysis, EMT, and inflammation. Sec13 knockdown suppressed these effects, alleviating ALI. Sec13 forms a protein complex with Pgm1, an enzyme regulating glucose-6-phosphate (G6P) production, and Ubqln1, an ubiquitin ligase. Sec13 inhibits Ubqln1-mediated Pgm1 ubiquitination, thereby stabilizing Pgm1. In ALI, Pgm1 binding to Sec13 increased but binding to Ubqln1 decreased. Sec13 knockdown decreased lactate, G6P, EMT markers, and inflammatory cytokines. Pgm1 knockdown produced similar effects. Ubqln1 overexpression suppressed inflammation but decreased Pgm1 expression. In conclusion, Sec13 plays a key role in ALI by inhibiting Ubqln1-mediated Pgm1 ubiquitination, affecting glycolysis and EMT. Sec13 and Pgm1 may be new targets for treating ALI.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sec13 promotes glycolysis by inhibiting Ubqln1 mediated Pgm1 ubiquitination in ALI\",\"authors\":\"\",\"doi\":\"10.1016/j.bbadis.2024.167475\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Acute lung injury (ALI) is a severe lung damage characterized by acute hypoxemia, increased pulmonary vascular permeability, and inflammatory reactions. Despite current treatments, mortality from ALI remains high. This study found that Sec13 is highly expressed in ALI and regulates it by glycolysis and epithelial-mesenchymal transition (EMT). In an ALI mouse model and cell model, Sec13 expression increased, accompanied by enhanced glycolysis, EMT, and inflammation. Sec13 knockdown suppressed these effects, alleviating ALI. Sec13 forms a protein complex with Pgm1, an enzyme regulating glucose-6-phosphate (G6P) production, and Ubqln1, an ubiquitin ligase. Sec13 inhibits Ubqln1-mediated Pgm1 ubiquitination, thereby stabilizing Pgm1. In ALI, Pgm1 binding to Sec13 increased but binding to Ubqln1 decreased. Sec13 knockdown decreased lactate, G6P, EMT markers, and inflammatory cytokines. Pgm1 knockdown produced similar effects. Ubqln1 overexpression suppressed inflammation but decreased Pgm1 expression. In conclusion, Sec13 plays a key role in ALI by inhibiting Ubqln1-mediated Pgm1 ubiquitination, affecting glycolysis and EMT. Sec13 and Pgm1 may be new targets for treating ALI.</p></div>\",\"PeriodicalId\":8821,\"journal\":{\"name\":\"Biochimica et biophysica acta. Molecular basis of disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-08-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochimica et biophysica acta. Molecular basis of disease\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0925443924004691\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular basis of disease","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0925443924004691","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
急性肺损伤（ALI）是一种以急性低氧血症、肺血管通透性增加和炎症反应为特征的严重肺损伤。尽管目前有多种治疗方法，但 ALI 的死亡率仍然很高。这项研究发现，Sec13在ALI中高表达，并通过糖酵解和上皮-间质转化（EMT）调节ALI。在 ALI 小鼠模型和细胞模型中，Sec13 的表达增加，并伴随着糖酵解、EMT 和炎症的增强。敲除 Sec13 可抑制这些影响，从而缓解 ALI。Sec13 与调节葡萄糖-6-磷酸（G6P）生成的酶 Pgm1 和泛素连接酶 Ubqln1 形成蛋白复合物。Sec13 可抑制 Ubqln1 介导的 Pgm1 泛素化，从而稳定 Pgm1。在 ALI 中，Pgm1 与 Sec13 的结合增加，但与 Ubqln1 的结合减少。Sec13基因敲除可减少乳酸、G6P、EMT标记物和炎症细胞因子。Pgm1 基因敲除也产生了类似的效果。Ubqln1 的过表达抑制了炎症，但降低了 Pgm1 的表达。总之，Sec13 通过抑制 Ubqln1 介导的 Pgm1 泛素化，影响糖酵解和 EMT，从而在 ALI 中发挥关键作用。Sec13 和 Pgm1 可能是治疗 ALI 的新靶点。
Sec13 promotes glycolysis by inhibiting Ubqln1 mediated Pgm1 ubiquitination in ALI
Acute lung injury (ALI) is a severe lung damage characterized by acute hypoxemia, increased pulmonary vascular permeability, and inflammatory reactions. Despite current treatments, mortality from ALI remains high. This study found that Sec13 is highly expressed in ALI and regulates it by glycolysis and epithelial-mesenchymal transition (EMT). In an ALI mouse model and cell model, Sec13 expression increased, accompanied by enhanced glycolysis, EMT, and inflammation. Sec13 knockdown suppressed these effects, alleviating ALI. Sec13 forms a protein complex with Pgm1, an enzyme regulating glucose-6-phosphate (G6P) production, and Ubqln1, an ubiquitin ligase. Sec13 inhibits Ubqln1-mediated Pgm1 ubiquitination, thereby stabilizing Pgm1. In ALI, Pgm1 binding to Sec13 increased but binding to Ubqln1 decreased. Sec13 knockdown decreased lactate, G6P, EMT markers, and inflammatory cytokines. Pgm1 knockdown produced similar effects. Ubqln1 overexpression suppressed inflammation but decreased Pgm1 expression. In conclusion, Sec13 plays a key role in ALI by inhibiting Ubqln1-mediated Pgm1 ubiquitination, affecting glycolysis and EMT. Sec13 and Pgm1 may be new targets for treating ALI.
期刊介绍：
BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.
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