Cells of the mononuclear phagocyte system (MPS) protect the host by clearing effete and foreign particulates from the circulation. The current study was designed to identify, quantify, harvest, and provide a partial functional characterization of the…
Mitochondria are the major source of reactive oxygen species. Both complex I and complex II mediate O2*- production in mitochondria and host reactive protein thiols. To explore the functions of the specific domains involved in the redox modifications…
Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and…
The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated to control bile acid synthesis and maintain lipid homeostasis. Recent studies in mice suggest that bile acid synthesis is regulated by the fasted-to-fed cycle, and fasting…
Cholesterol 7 alpha-hydroxylase (CYP7A1) of the bile acid biosynthesis pathway is suppressed by bile acids and inflammatory cytokines. Bile acids are known to induce inflammatory cytokines to activate the mitogen-activated protein kinase/c-Jun…
UNLABELLED: Bile acid synthesis in the liver is regulated by the rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1). Transcription of the CYP7A1 gene is inhibited by bile acids and cytokines. The rate of bile acid synthesis is reduced…
UNLABELLED: Mouse fibroblast growth factor 15 (FGF15) and human ortholog FGF19 have been identified as the bile acid-induced intestinal factors that mediate bile acid feedback inhibition of cholesterol 7alpha-hydroxylase gene (C YP7A1) transcription…
UNLABELLED: Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway that converts cholesterol into bile acids in the liver. Recent studies have shown that bile acids may play an important role in…
UNLABELLED: We reported previously that mice overexpressing cytochrome P450 7a1 (Cyp7a1; Cyp7a1-tg mice) are protected against high fat diet-induced hypercholesterolemia, obesity, and insulin resistance. Here, we investigated the underlying mechanism…
UNLABELLED: Bile acid synthesis not only produces physiological detergents required for intestinal nutrient absorption, but also plays a critical role in regulating hepatic and whole-body metabolic homeostasis. We recently reported that…
UNLABELLED: Mice deficient in small heterodimer partner (SHP) are protected from diet-induced hepatic steatosis resulting from increased fatty acid oxidation and decreased lipogenesis. The decreased lipogenesis appears to be a direct consequence of…
UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is one of the major health concerns worldwide. Farnesoid X receptor (FXR) is considered a therapeutic target for treatment of NAFLD. However, the mechanism by which activation of FXR lowers hepatic…
UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). So far, the underlying mechanism remains poorly understood. Here, we show that hepatic…
Bile acids are signaling molecules that play a critical role in regulation of hepatic metabolic homeostasis by activating nuclear farnesoid X receptor (Fxr) and membrane G-protein-coupled receptor (Takeda G-protein-coupled receptor 5; Tgr5). The role…
UNLABELLED: Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases…
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important regulators of bile acid, lipid, and glucose homeostasis. Here, we show that global Fxr (-/-) Shp(-/-) double knockout (DKO) mice are refractory to weight…
Bile acids activate farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (aka Takeda G protein-coupled receptor-5 [TGR5]) to regulate bile acid metabolism and glucose and insulin sensitivity. FXR and TGR5 are coexpressed in the…
Activation of the nuclear bile acid receptor farnesoid X receptor (FXR) protects against hepatic inflammation and injury, while Takeda G protein-coupled receptor 5 (TGR5) promotes adipose tissue browning and energy metabolism. Here, we examined the…
This study investigated the role of ethanol-inducible cytochrome P450-2E1 (CYP2E1) in enhancing CYP2E1 and other P450 proteins in extracellular vesicles (EVs) from alcohol-exposed rodents and human patients with alcoholism and their effects on…
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a master regulator for white adipocyte differentiation and lipid storage. The increased level of hepatic PPARgamma2 isoform reprograms liver for lipid storage and causes abnormal fat…
Alcoholic fatty liver disease (AFLD) is a major risk factor for cirrhosis-associated liver diseases. Studies demonstrate that alcohol increases serum bile acids in humans and rodents. AFLD has been linked to cholestasis, although the physiologic…
Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that…
Persistent infection with oncogenic human papillomaviruses (HPVs) is the most important factor in the induction of uterine cervical cancer, a leading cause of cancer mortality in women worldwide. Upon cell transformation, continual expression of the…
Transplantation of adult stem cells into myocardial tissue after acute myocardial infarction (AMI), has been shown to improve tissue recovery and prevent progression to ischemic cardiomyopathy. Studies suggest that the effects of mesenchymal stem…
Diabetes is a risk factor for worse outcomes following acute myocardial infarction (AMI). In this study, we tested the hypothesis that SDF-1:CXCR4 expression is compromised in post-AMI in diabetes, and that reversal of this defect can reverse the…
The expression of the rat cytochrome P450 CYP4 family was studied in hepatic tumors. In most of the primary and transplantable hepatic tumors studied, lauric acid omega-hydroxylase activity associated with the CYP4A subfamily enzymes decreased. The…
Cholesterol 7 alpha-hydroxylase is the rate limiting enzyme in bile acid biosynthesis and plays an important role in cholesterol homeostasis. The Golden Syrian hamster has been used as an animal model for the study of atherosclerosis and cholesterol…
The human liver CYP4F2 gene (Accession No. AF221943) encodes a leukotriene B(4) omega-hydroxylase that metabolizes leukotriene B(4) (LTB(4)) to a less potent proinflammatory eicosanoid, 20-OH-LTB(4). We sequenced a 6.7-kb genomic fragment of the…
The expression of cholesterol 7 alpha-hydroxylase mRNA levels in confluent HepG2 cultures was reduced by tauro- or glyco-conjugates of deoxycholate and chenodeoxycholate, but not by cholate. Ursodeoxycholates, on the other hand, stimulated the mRNA…
The activity of the rat CYP7A/luciferase reporter gene was increased five-fold by all-trans retinoic acid (atRA) or 9-cis retinoic acid (9cRA) in transient transfection assay in HepG2 cells. Cotransfection with retinoid X receptor (RXR) stimulated…
Cholesterol 7 alpha-hydroxylase catalyzes the first and rate-limiting step in the conversion of cholesterol to bile acids in the liver. Previously, we have identified two bile acid response elements located in nt -74 to -54 (BARE-I) and -148 to -118…
The human CYP4F2 gene encodes a LTB4 omega-hydroxylase P450 prominently expressed in liver and kidney that functions to metabolize and inactivate the pro-inflammatory eicosanoids, LTB4 and arachidonic acid. HepG2 cells transfected with CYP4F2 -506/-6…
The human cholesterol 7 alpha-hydroxylase gene (CYP7) spans about 11 kb of the genome and contains six exons and five introns. Nucleotide sequences of a 5'-upstream region to exon III (5535 bp), a 5'-upstream EcoRI fragment (2575 bp), and an EcoRI…
Human papillomavirus (HPV) type 18 DNA was found in an aggressively invasive adenocarcinoma tumor from a woman who had an intact hymen and denied any prior sexual intercourse. The viral DNA was detected within the tumor tissue by polymerase chain…
The 4070A amphotropic murine leukemia virus (A-MuLV) has been variably reported to harbor neurovirulence determinants within its env gene. In this report we reexamined this issue by applying two approaches previously demonstrated to amplify murine…
Deep tissue wound healing requires a complex sequence of several factors working in unison to repair the organ at risk. Myocardial infarction (MI) is particularly complex due to several local and systemic factors mediating the repair process within…
