对转录因子EB进行向,以抑制自-溶酶体功能,有助于急性损伤
Peng-Fei Dong1, Tian-Bin Liu2, Kai Chen2
1College of Veterinary Medicine, Shandong Provincial Key Laboratory of Zoonoses, Shandong Agricultural University, 7 Panhe Street, Tai'an City, 271017, Shandong Province, China.
Journal of advanced research
|July 21, 2024
概括
暴露于会通过抑制自和溶酶体功能而导致急性损伤 (AKI). 激活转录因子EB (TFEB) 对这种损伤进行保护,强调TFEB是诱导的AKI的潜在治疗标.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 环境和职业 (Cd) 暴露是已知的急性损伤 (AKI) 的原因之一.
- 自抑制和溶酶体功能障碍是Cd诱导的AKI的关键机制.
研究的目的:
- 调查转录因子EB (TFEB) 的作用,这是自-溶酶体功能的调节剂,在Cd诱导的AKI中.
- 阐明TFEB通过哪些机制影响Cd诱导的损伤.
主要方法:
- 在体内和体外的研究使用Cd诱导的AKI模型进行.
- 分析了TFEB表达,核转位,酸化和乙化.
- 使用了TFEB,mTORC1,CRM1和GCN5的药理学和基因操纵.
主要成果:
- Cd诱导的AKI与TFEB表达和核转位的减少有关,以及自-溶酶体功能受损.
- TFEB激活改善了Cd诱导的AKI,而TFEB倒置则使其恶化.
- Cd通过mTORC1和CRM1诱导了TFEB酸化和核输出,并通过GCN5介导的乙化降低了TFEB转录活性.
结论:
- 通过调节自-溶酶体功能,TFEB在缓解Cd诱导的AKI方面发挥着至关重要的作用.
- 通过酸化,核出口和乙化,Cd抑制了TFEB活动.
- 针对TFEB激活是一种有前途的治疗策略,用于治疗Cd诱导的AKI.
更多相关视频
相关概念视频
Autophagy
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Acute Kidney Injury II: Pathophysiology
Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
Acute Kidney Injury IV: Diagnostic Studies and Prevention
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Acute Pancreatitis II: Pathophysiology
The pathophysiology of acute pancreatitis centers on injury to pancreatic acinar cells, which initiates a cascade of harmful intracellular events.This injury leads to premature activation of trypsinogen to trypsin in the pancreas. Trypsin then activates other digestive enzymes, such as chymotrypsin, elastase, and phospholipase A2, which begin breaking down pancreatic tissue. The resulting autodigestion causes local inflammation, tissue swelling, hemorrhage, and fat necrosis.Injured acinar cells...


