Colin T. Shearn
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View article: Inflammatory Oxidative Stress Compounds Inhibit Insulin Secretion through Rapid Protein Carbonylation
Inflammatory Oxidative Stress Compounds Inhibit Insulin Secretion through Rapid Protein Carbonylation Open
Pancreatic β-cells in pre-type 1 diabetes (T1D) experience stress due to islet inflammation, which accompanies early defects in insulin secretion that precede autoimmune destruction. One product of inflammatory stress is protein carbonylat…
View article: Abstract 2481 Inhibition of Insulin Secretion Induced by Oxidative Stress Compounds
Abstract 2481 Inhibition of Insulin Secretion Induced by Oxidative Stress Compounds Open
View article: Transcriptional analysis of murine biliary atresia identifies macrophage heterogeneity and subset-specific macrophage functions
Transcriptional analysis of murine biliary atresia identifies macrophage heterogeneity and subset-specific macrophage functions Open
Introduction Macrophages play an important role in disease progression of pediatric cholestatic liver disease, particularly biliary atresia (BA); however, the restorative versus pathogenic role for precise macrophage subsets remains poorly…
View article: Overexpression of TNFα in TNF∆ARE+/− mice increases hepatic periportal inflammation and alters bile acid signaling in mice
Overexpression of TNFα in TNF∆ARE+/− mice increases hepatic periportal inflammation and alters bile acid signaling in mice Open
Background: Intestinal inflammation is a common factor in ~70% of patients diagnosed with primary sclerosing cholangitis. The TNF ∆ARE+/− mouse overexpresses TNFα and spontaneously develops ileitis after weaning. The aim of this study was …
View article: Expression of circadian regulatory genes is dysregulated by increased cytokine production in mice subjected to concomitant intestinal injury and parenteral nutrition
Expression of circadian regulatory genes is dysregulated by increased cytokine production in mice subjected to concomitant intestinal injury and parenteral nutrition Open
Background We have developed a mouse model of Parenteral Nutrition Associated Cholestasis (PNAC) in which combining intestinal inflammation and PN infusion results in cholestasis, hepatic macrophage activation, and transcriptional suppress…
View article: Endocrine pancreas-specific<i>Gclc</i>gene deletion causes a severe diabetes phenotype
Endocrine pancreas-specific<i>Gclc</i>gene deletion causes a severe diabetes phenotype Open
Reduced glutathione (GSH) is an abundant antioxidant that regulates intracellular redox homeostasis by scavenging reactive oxygen species (ROS). Glutamate-cysteine ligase catalytic (GCLC) subunit is the rate-limiting step in GSH biosynthes…
View article: Thioredoxin reductase 1 regulates hepatic inflammation and macrophage activation during acute cholestatic liver injury
Thioredoxin reductase 1 regulates hepatic inflammation and macrophage activation during acute cholestatic liver injury Open
Background and Aims: Cholestatic liver diseases, including primary sclerosing cholangitis, are characterized by periportal inflammation with progression to hepatic fibrosis and ultimately cirrhosis. We recently reported that the thioredoxi…
View article: The autophagic protein p62 is a target of reactive aldehydes in human and murine cholestatic liver disease
The autophagic protein p62 is a target of reactive aldehydes in human and murine cholestatic liver disease Open
Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative …
View article: NF‐κB Regulation of LRH‐1 and ABCG5/8 Potentiates Phytosterol Role in the Pathogenesis of Parenteral Nutrition–Associated Cholestasis
NF‐κB Regulation of LRH‐1 and ABCG5/8 Potentiates Phytosterol Role in the Pathogenesis of Parenteral Nutrition–Associated Cholestasis Open
Background and Aims Chronically administered parenteral nutrition (PN) in patients with intestinal failure carries the risk for developing PN‐associated cholestasis (PNAC). We have demonstrated that farnesoid X receptor (FXR) and liver X r…
View article: Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach
Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach Open
1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States. Although it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Ve…
View article: Supplemental Ascorbate Diminishes DNA Damage Yet Depletes Glutathione and Increases Acute Liver Failure in a Mouse Model of Hepatic Antioxidant System Disruption
Supplemental Ascorbate Diminishes DNA Damage Yet Depletes Glutathione and Increases Acute Liver Failure in a Mouse Model of Hepatic Antioxidant System Disruption Open
Cellular oxidants are primarily managed by the thioredoxin reductase-1 (TrxR1)- and glutathione reductase (Gsr)-driven antioxidant systems. In mice having hepatocyte-specific co-disruption of TrxR1 and Gsr (TrxR1/Gsr-null livers), methioni…
View article: Multivalent lipid targeting by the calcium-independent C2A domain of synaptotagmin-like protein 4/granuphilin
Multivalent lipid targeting by the calcium-independent C2A domain of synaptotagmin-like protein 4/granuphilin Open
Synaptotagmin-like protein 4 (Slp-4), also known as granuphilin, is a Rab effector responsible for docking secretory vesicles to the plasma membrane before exocytosis. Slp-4 binds vesicular Rab proteins via an N-terminal Slp homology domai…
View article: Bile acids modulate colonic MAdCAM-1 expression in a murine model of combined cholestasis and colitis
Bile acids modulate colonic MAdCAM-1 expression in a murine model of combined cholestasis and colitis Open
View article: Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function
Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function Open
Two Supplemental figures for manuscript: "Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function"
View article: Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function
Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function Open
Two Supplemental figures for manuscript: "Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function"
View article: Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function
Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function Open
Two Supplemental figures for manuscript: "Pathogenesis of Murine Cholestatic Liver Disease Associated with Sex-Related Differences in Hepatic Natural Killer Cell Subsets and Function"
View article: 4‐Hydroxy‐2‐nonenal attenuates 8‐oxoguanine DNA glycosylase 1 activity
4‐Hydroxy‐2‐nonenal attenuates 8‐oxoguanine DNA glycosylase 1 activity Open
Elevated cellular oxidative stress and oxidative DNA damage are key contributors to impaired cardiac function in diabetes. During chronic inflammation, reactive oxygen species (ROS)‐induced lipid peroxidation results in the formation of re…
View article: Multivalent lipid targeting by the calcium-independent C2A domain of Slp-4/granuphilin
Multivalent lipid targeting by the calcium-independent C2A domain of Slp-4/granuphilin Open
Synaptotagmin-like protein 4 (Slp-4), also known as granuphilin, is a Rab effector responsible for docking secretory vesicles to the plasma membrane before exocytosis. Slp-4 binds vesicular Rab proteins via an N-terminal Slp homology (SHD)…
View article: Cholestatic liver disease results increased production of reactive aldehydes and an atypical periportal hepatic antioxidant response
Cholestatic liver disease results increased production of reactive aldehydes and an atypical periportal hepatic antioxidant response Open
View article: TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy
TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy Open
Thioredoxin reductase-1 (TrxR1)-, glutathione reductase (Gsr)-, and Nrf2 transcription factor-driven antioxidant systems form an integrated network that combats potentially carcinogenic oxidative damage yet also protects cancer cells from …
View article: Quantifying Competition among Mitochondrial Protein Acylation Events Induced by Ethanol Metabolism
Quantifying Competition among Mitochondrial Protein Acylation Events Induced by Ethanol Metabolism Open
Mitochondrial dysfunction is one of many key factors in the etiology of alcoholic liver disease (ALD). Lysine acetylation is known to regulate numerous mitochondrial metabolic pathways, and recent reports demonstrate that alcohol-induced p…
View article: Lipid peroxidation derived reactive aldehydes in alcoholic liver disease
Lipid peroxidation derived reactive aldehydes in alcoholic liver disease Open
View article: Elevated Nrf-2 responses are insufficient to mitigate protein carbonylation in hepatospecific PTEN deletion mice
Elevated Nrf-2 responses are insufficient to mitigate protein carbonylation in hepatospecific PTEN deletion mice Open
Results show that disruption of PTEN resulted in steatohepatitis, fibrosis and caused hepatic induction of the Nrf2-dependent antioxidant system at least in part due to elevation of p62. This response was both cell-type and zone specific. …
View article: Knockout of the <i>Gsta4</i> Gene in Male Mice Leads to an Altered Pattern of Hepatic Protein Carbonylation and Enhanced Inflammation Following Chronic Consumption of an Ethanol Diet
Knockout of the <i>Gsta4</i> Gene in Male Mice Leads to an Altered Pattern of Hepatic Protein Carbonylation and Enhanced Inflammation Following Chronic Consumption of an Ethanol Diet Open
Background Glutathione S‐transferase A4‐4 ( GSTA 4) is a key enzyme for removal of toxic lipid peroxidation products such as 4‐hydroxynonenal (4‐ HNE ). In this study, we examined the potential role of GSTA 4 on protein carbonylation and p…
View article: Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 Congress
Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 Congress Open
The symposium, “Role of Nutrition in Alcoholic Liver Disease”, was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances a…
View article: Dysregulation of antioxidant responses in patients diagnosed with concomitant Primary Sclerosing Cholangitis/Inflammatory Bowel Disease
Dysregulation of antioxidant responses in patients diagnosed with concomitant Primary Sclerosing Cholangitis/Inflammatory Bowel Disease Open
View article: S09-3ROLE OF FAT/CARBOHYDRATE RATIO AND DIETARY FAT TYPE IN DEVELOPMENT OF ALCOHOLIC PATHOLOGY
S09-3ROLE OF FAT/CARBOHYDRATE RATIO AND DIETARY FAT TYPE IN DEVELOPMENT OF ALCOHOLIC PATHOLOGY Open
View article: Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation
Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation Open
Overall, the findings presented in this study support a role for EtOH-induced lysine acetylation as an adverse posttranslational modification within the mitochondria that directly impacts SOD2 charge state and activity. Last, the data pres…
View article: Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase
Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase Open
View article: Global Deletion of Glutathione S-Transferase A4 Exacerbates Developmental Nonalcoholic Steatohepatitis
Global Deletion of Glutathione S-Transferase A4 Exacerbates Developmental Nonalcoholic Steatohepatitis Open