Searching across hundreds of databases
Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis (NASH) in response to elevated endoplasmic reticulum (ER) stress. Whereas the onset of simple steatosis requires elevated de novo lipogenesis, progression to NASH is triggered by accumulation of hepatocyte-free cholesterol. We now show that caspase-2, whose expression is ER-stress inducible and elevated in human and mouse NASH, controls the buildup of hepatic-free cholesterol and triglycerides by activating sterol regulatory element-binding proteins (SREBP) in a manner refractory to feedback inhibition. Caspase-2 colocalizes with site 1 protease (S1P) and cleaves it to generate a soluble active fragment that initiates SCAP-independent SREBP1/2 activation in the ER. Caspase-2 ablation or pharmacological inhibition prevents diet-induced steatosis and NASH progression in ER-stress-prone mice. Caspase-2 inhibition offers a specific and effective strategy for preventing or treating stress-driven fatty liver diseases, whereas caspase-2-generated S1P proteolytic fragments, which enter the secretory pathway, are potential NASH biomarkers.
Pubmed ID: 30220454 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsThis polyclonal targets IRS-2 (L1326)
View all literature mentionsThis polyclonal targets P4HB
View all literature mentionsThis polyclonal targets Insig1 antibody
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis monoclonal targets Myc Tag
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis polyclonal targets UCP1
View all literature mentionsThis polyclonal targets PARP1, PARP2
View all literature mentionsThis monoclonal targets cHMGCS (H-9)
View all literature mentionsThis monoclonal targets Fatty Acid Synthase
View all literature mentionsThis polyclonal targets Acetyl CoA Carboxylase
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis polyclonal targets PRKAA1, PRKAA2
View all literature mentionsThis monoclonal targets AMPK-alpha, phospho (Thr172)
View all literature mentionsThis monoclonal targets SKI-1 (A-11)
View all literature mentionsThis polyclonal targets SREBP2
View all literature mentionsThis monoclonal targets SREBP1
View all literature mentionsThis polyclonal targets p62
View all literature mentionsThis polyclonal targets active Caspase 2
View all literature mentionsThis monoclonal targets CASP2
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name B6.129S4-Casp2tm1Yuan/J from IMSR.
View all literature mentionsThis monoclonal targets AMPK-alpha, phospho (Thr172)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
