Western blottings of liver homogenate (40 g/lane) were probed with antibodies to EGR-1 (= 3C4). mRNAs levels, of EtOH-metabolizing enzymes, including alcohol dehydrogenase 1, aldehyde dehydrogenase 1A1, and catalase, as well as the microsomal triglyceride transfer protein, involved in regulating lipid output were higher in gene in rodents, human primary hepatocytes, and human liver samples of alcoholics (43,C45). Currently, little is known regarding the molecular mechanism of PXR-mediated activation of EtOHCinduced steatosis. In this study, male WT and and = 6C7). = 7)= 7)= 6)= 7) 0.05 was between mice fed control diet and EtOH. 0.05 was between mice fed EtOH. Open in a separate window Figure 1. Characterization of hepatic histology and hepatic lipids in male WT and = 5C6). #, 0.05 between mice fed control diet and EtOH. ?, 0.05 between mice fed EtOH. Chronic EtOH ingestion significantly up-regulated mRNA levels of PXR and CAR and CAR target gene Cyp2b10 in WT mice Chronic EtOH ingestion significantly up-regulated mRNA expression (1.8-fold) in WT mice, but not in mRNA in the mRNA levels did not vary between WT and gene expression does not appear to be dependent on PXR but that EtOHCinduced up-regulation of mRNA might be. Chronic EtOH exposure induced the hepatic mRNA 2.9-fold only in WT mice (Fig. 2and small heterodimer partner (and and mRNA levels, each by SDZ 220-581 Ammonium salt 61% in WT mice compared with their respective control-fed mice. In contrast, EtOH decreased mRNA by 40% but not mRNA levels in and gene (1.6-fold) in WT mice Mouse monoclonal to LPL and had no effect in ((47) were lower, 39 and 57%, respectively, compared with their respective WT controls (Fig. 2, and and mRNA levels in mRNA levels by 69% in WT mice without any effect on mRNA levels (Fig. 2, and mRNA levels did not differ between the two genotypes (Fig. 2mRNA expression by about 3-fold in WT mice, the mRNA of its target gene was increased dramatically (about 220-fold) in WT mice but not in EtOH-fed and gene expression by EtOH, CYP2B10 protein levels were SDZ 220-581 Ammonium salt significantly higher in EtOH-fed WT mice (27-fold) compared with WT controls (Fig. 2(((mRNAs were quantified as described under Experimental procedures. Data represent mean S.D. (= 4C6). Furthermore, Western blottings of liver homogenate (40 g/lane) were probed with antibodies to CYP2B10 (and = 3C4). *, 0.05 between WT and 0.05 between mice fed control diet and EtOH. ?, 0.05 between mice fed EtOH. PXR deficiency suppresses chronic EtOHCinduced lipogenic gene induction The steatosis observed in EtOH-fed WT mice prompted us to examine the expression of and early growth response-1 (mRNA levels were higher (1.9-fold) in control-fed mRNA levels in WT mice (1.6-fold) compared with control-fed WT mice (Fig. 3mRNA levels by 48% in mRNAs in both genotypes (Fig. 3, mRNA (2.9-fold) only in WT mice (Fig. 3mRNA levels did not vary between the two genotypes, and their mRNA levels were not different after EtOH treatment (Fig. 3mRNA and SDZ 220-581 Ammonium salt protein levels did not vary between the two genotypes. However, EtOH treatment significantly increased mRNA (3.2-fold) and protein (12.3-fold) levels only in WT mice (Fig. 3, and (mRNAs were quantified as described under Experimental procedures. Data represent mean S.D. (= 4C6). Western blottings of liver homogenate (40 g/lane) were probed with antibodies to EGR-1 (= 3C4). *, 0.05 between WT and 0.05 between mice fed control diet and EtOH. ?,.