In this article, we report on the expression and function of a Na(+)-coupled transporter for citrate, NaCT, in human and rat liver cell lines and in primary hepatocytes from the rat liver. We also describe the polarized expression of this transporter in human and rat livers. Citrate uptake in human liver cell lines HepG2 and Huh-7 was obligatorily dependent on Na+. The uptake system showed a pr...

Retained bile acids, which are capable of inducing cell death, activate protein kinase Cδ (PKC-δ) in hepatocytes. In nonhepatic cells, both pro- and antiapoptotic effects of PKC-δ are described. The aim of this study was to determine the role of PKC-δ in glycochenodeoxycholate (GCDC)-induced apoptosis in rat hepatocytes and human HUH7-Na-taurocholate-cotransporting polypeptide (Ntcp) cells. Apo...

CYP2E1-inducing capacity of xenobiotics was determined in cultured hepatocytes on the basis of enzyme activities (chlorzoxazone 6-hydroxylation and 7-ethoxycoumarin O-dealkylation) and protein levels. Hepatocytes in culture showed rapid loss of CYP2E1 enzyme during 72 h. CYP2E1 inducers (ethanol, dimethyl sulfoxide, acetone, isopropanol, pyrazole, and imidazole) were able to prevent the fast de...

The metabolism of sameridine (LPB) (an amide-type local anesthetic-analgesic agent with a hexyl side chain) to carboxylic acid derivatives by isolated male rat hepatocytes was studied using gradient reversed-phase HPLC and mass spectrometry. Incubation of sameridine with hepatocytes resulted in the formation of numerous different metabolites. Two carboxylic acids, i.e., the C(6) and C(4) carbox...

UNLABELLED Excessive hepatocyte apoptosis is a common event in acute and chronic liver diseases leading to loss of functional liver tissue. Approaches to prevent apoptosis have therefore high potential for the treatment of liver disease. G-protein coupled receptors (GPCR) play crucial roles in cell fate (proliferation, cell death) and act through heterotrimeric G-proteins. G(αi)PCRs have been s...

OBJECTIVE In normal subjects, the major form of circulating IGF is the GH-dependent 150 kDa complex. The liver appears to be the main source of the three components of the 150 kDa complex and, in particular, hepatocytes synthesize the insulin-like growth factor (IGF) peptide and the acid-labile subunit (ALS), whereas Kupffer and sinusoidal endothelial cells produce IGF-binding protein-3 (IGFBG-...

Chloroacetonitrile (CAN) is a disinfectant by-product of drinking water chlorination. The present work was designed to investigate the cytotoxic effects as well as the oxidative stress induced by CAN in isolated rat hepatocytes. Hepatocytes were exposed to different concentrations of CAN (5–40 μM) in a time-course experiment for up to 2 h. CAN exposure induced a significant decrease in cell via...

The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) decreases cytochrome P-450 (CYP) expression in rat hepatocytes. Because IL-2 increases c-Myc in lymphocytes and because c-myc overexpression represses several genes, we postulated that the IL-2/IL-2R interaction may increase c-Myc and thereby down-regulate CYP in hepatocytes. Cultured rat hepatocytes were exposed for 24 h to IL-2...

To establish a predictive in vitro cardiovascular toxicity and hepatotoxicity screening system, whole cells from the neonatal rat heart and rat hepatocytes were cultured with known cardiotoxic and hepatotoxic compounds and cytotoxicities were assessed. The heart cells were isolated from neonatal SD rats by enzyme digestion and cultured on type I collagen gel. After a several days of preculture,...

The mechanism for hepatic uptake of temocaprilat, an angiotensin-converting enzyme inhibitor that is predominantly excreted into bile was studied using isolated rat hepatocytes and COS-7 cells expressing the organic anion transporting polypeptide (oatp1). The uptake of temocaprilat into isolated rat hepatocytes exhibited saturation with a Km of 20.9 microM and a Vmax of 0.21 nmol/min/mg protein...