A5005429193- Glycosylation and Glycoproteins Research
- Liver physiology and pathology
- Galectins and Cancer Biology
- Drug-Induced Hepatotoxicity and Protection
- Carbohydrate Chemistry and Synthesis
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Microbial metabolism and enzyme function
- Protein Tyrosine Phosphatases
- Autophagy in Disease and Therapy
- Per- and polyfluoroalkyl substances research
- Cannabis and Cannabinoid Research
- Biochemical Analysis and Sensing Techniques
- Hepatitis C virus research
- Birth, Development, and Health
- Cancer Research and Treatments
- Chromosomal and Genetic Variations
- Sirtuins and Resveratrol in Medicine
- Adipose Tissue and Metabolism
- Genomics and Phylogenetic Studies
- Regulation of Appetite and Obesity
- Lysosomal Storage Disorders Research
- Ubiquitin and proteasome pathways
- Telomeres, Telomerase, and Senescence
Sekisui XenoTech (United States)
2024
Quality Biological
2024
University of Kansas Medical Center
2015-2021
Inhibiting acute injury–induced senescence mediated by TGFβ signaling in regenerative epithelium improves liver regeneration.
Background & AimsThe liver has a unique capacity to regenerate after injury in highly orchestrated and regulated manner. Here, we report that O-GlcNAcylation, an intracellular post-translational modification by 2 enzymes, O-GlcNAc transferase (OGT) O-GlcNAcase (OGA), is critical termination signal for regeneration following partial hepatectomy (PHX).MethodsWe studied PHX on hepatocyte specific OGT OGA knockout mice (OGT-KO OGA-KO), which caused significant decrease (OGT-KO) increase (OGA-KO)...
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role a posttranslational modification proteins called O-GlcNAcylation, where O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes single β-D-N-acetylglucosamine (O-GlcNAc) moiety, pathogenesis APAP-induced injury. Hepatocyte-specific OGT knockout mice (OGT KO), which reduced wild-type (WT) controls were treated with 300 mg/kg APAP development injury was studied over time course from 0 to 24 h....
Abstract Like many per- or polyfluorinated alkyl substances (PFAS), toxicity studies with HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate), a short-chain PFAS used in the manufacture of some types fluorinated polymers, indicate that liver is primary target rodents following oral exposure. Although current weight evidence supports PPARα mode action (MOA) for effects HFPO-DA-exposed mice, alternate MOAs have also been hypothesized including PPARγ cytotoxicity. To...
Abstract Recent in vitro transcriptomic analyses for the short-chain polyfluoroalkyl substance, HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate), support conclusions from vivo data that HFPO-DA-mediated liver effects mice are part of early key events peroxisome proliferator-activated receptor alpha (PPARα) activator-induced rodent hepatocarcinogenesis mode action (MOA). Transcriptomic responses HFPO-DA-treated hepatocytes have high concordance with those treated a...
Estrogen receptor alpha (ESR1) is 1 of the 2 intracellular receptors for estrogen and expressed by hepatocytes in liver. The role ESR1 regulation toxicant-induced liver injury compensatory regeneration not completely clear. We investigated after carbon tetrachloride (CCl 4 )-induced using wild type (WT) knockout (ESR1-KO) rats. Adult female WT ESR1-KO rats were treated with mL/kg CCl euthanized over a time course 0 to 48 hours. Liver measured serum alanine amino transaminase,...
Caloric need has long been thought a major driver of appetite. However, it is unclear whether caloric regulates appetite in environments offered by many societies today where there no shortage food. Here we observed that wildtype mice with free access to food did not match calorie intake expenditure. While the size meal affected subsequent intake, was compensation for earlier under- or over-consumption. To test how spontaneous eating subject control, manipulated O-linked...
Abstract Pharmacologic or genetic manipulation of O-GlcNAcylation, an intracellular, single sugar post-translational modification, are difficult to interpret due the pleotropic nature O-GlcNAc and vast signaling pathways it regulates. To address this issue, we employed either OGT (O-GlcNAc transferase), OGA (O-GlcNAcase) liver knockouts, pharmacological inhibition coupled with multi-Omics analysis bioinformatics. We identified numerous genes, proteins, phospho-proteins, metabolites that were...
O‐linked N‐Acetylglucosamine, more commonly referred to as O‐GlcNAc, is a single glycosidic post‐translational modification. OGT (O‐GlcNAc Transferase) and OGA (O‐GlcNAcase) are the sole enzymes responsible for addition (O‐GlcNAcylation) removal of respectively. OGA, present in all multicellular organisms organ tissues. Importantly, knockouts embryonically lethal, demonstrating requirement O‐GlcNAcylation early organismal development. Like most intracellular modifications, O‐GlcNAc regulates...
Abstract The liver has a unique capacity to regenerate after injury in highly orchestrated and regulated manner. Here we report that O-GlcNAcylation, an intracellular post-translational modification (PTM) by two enzymes, O-GlcNAc transferase (OGT) O-GlcNAcase (OGA), is critical termination signal for regeneration (LR) following partial hepatectomy (PHX). We studied PHX on hepatocyte specific OGT OGA knockout mice (OGT-KO OGA-KO), which caused significant decrease (OGT-KO) increase (OGA-KO)...
Objective To identify novel autophagy modulators using a high throughput image‐based screening and to explore their mechanisms of regulation the application for drug‐induced liver injury. Methods The library pharmacologically active compounds (LOPAC) was screened in mouse embryonic fibroblasts (MEFs) stably expressing GFP‐LC3. Compounds were tested at different concentrations with or without lysosome inhibitor chloroquine (CQ), GFP‐LC3 puncta quantified measure autophagic flux. Mechanisms...
Estrogen receptor alpha (Esr1) is one of the two cognate receptors for and expressed by hepatocytes. The role ESR1 in liver regeneration not completely clear. We studied after CCl 4 ‐induced injury using type (WT) knockout (ESR1‐KO) rats. Two‐three month old female WT ESR1‐KO rats were treated with 1ml/kg euthanized over a time course 0–48 hr. Liver Injury measured serum ALT histopathology increased substantially treatment but no significant difference between was noted. H&E staining...
O‐linked N ‐acetylglucosamine (O‐GlcNAc) is the attachment of a single β‐N‐acetylglucosamine to serine/threonine amino acid residues nuclear, cytoplasmic, and mitochondrial proteins. The modification sensitive changes in cellular environment dynamically regulated by opposing functions two specific enzymes; O‐GlcNAc transferase (OGT) adds modification, whereas, O‐GlcNAcase (OGA) removes it. Disruptions cycling contribute diseases such as neurodegeneration. Dysfunctional mitochondria lead...
Overdose of acetaminophen (APAP), the most widely used analgesic, results in acute liver failure. We have investigated role a post‐translational modification proteins called O‐GlcNAcylation pathogenesis APAP‐induced injury, where single β‐D‐N‐acetylglucosamine (O‐GlcNAc) moiety is added to by an enzyme O‐GlcNAc transferase (OGT) and removed O‐GlcNAcase (OGA). Male C57BL/6J mice were treated with 300 mg/kg APAP followed Thiamet‐G (TMG, 400 mg/kg) specific inhibitor OGA that induces...
Background O‐GlcNAcylation is a posttranslational modification where single N‐acetyl glucosamine (O‐GlcNAc) sugar added to Ser/Thr residue of protein catalyzed by an enzyme called GlcNAc transferase (OGT). plays significant role in cell proliferation, signaling and cancer pathogenesis. We investigated the liver regeneration after partial hepatectomy (PH) using hepatocyte specific OGT knockout (OGTKO) mice. Methods Two‐three month old male WT OGTKO mice were subjected PH samples collected...