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Interactions between tumor cells and their host environment can play a major role in regulating survival programs required for tumor progression. Osteopontin (OPN) is a glycophosphoprotein overexpressed by tumors, and is a key molecule for tumor progression and metastasis. OPN also inhibits expression of autocrine and paracrine inducible nitric oxide synthase (iNOS). Given the cytotoxic effects of...
Redox-mediated upregulation of transcription of hepatocyte inducible nitric oxide synthase (iNOS) requires hepatocyte nuclear factor IV-alpha (HNF-4α). In this setting, PC4 is often isolated with HNF-4α in DNA-protein pull-down studies. Transcriptional coactivator PC4 facilitates activator-dependent transcription via interactions with basal transcriptional machinery that are independent of PC4-DNA...
Background: The purpose of this study was to define the redox sensitive cis-acting transcriptional mechanisms that regulate inducible nitric oxide synthase (iNOS) promoter function in the hepatocyte. Methods: Clonal deletion constructs of the rat hepatocyte iNOS promoter (Genbank X95629; 1845 base pair)–reporter plasmid were transiently transfected into HepG2 cells treated with IL-1β and IL-1β + hydrogen...
Background: Nitric oxide (NO) regulates a variety of cellular functions. One mechanism by which NO may exert its influence is through formation of S-nitrosothiols at critical thiol residues in protein-active sites, including those of nuclear protein transcription factors. Methods: NF-κB p50 and AP-1 c-jun were S-nitrosylated in the presence of acidic NaNO 2 . Wild-type protein and protein...
Background. Nitric oxide (NO) is a ubiquitous multifunctional free radical produced during sepsis, shock, reperfusion injury, and allograft rejection. Many studies are presently evaluating the functional roles of NO production in these settings. However, the signal transduction mechanisms underlying initiation of NO production are largely unknown. This study defines the cell surface receptor proteins...
Background. A major impediment to kidney transplantation is the current shortage of donor organs. Currently approximately 22,500 candidates are awaiting kidney transplantation, while the number of donors remains stable at approximately 3500 each year in the United States. Alternative approaches to traditional organ donor selection are necessary. In this setting we hypothesized that kidneys with reduced...
Background. In a system of rat hepatocytes in primary culture, inhibition of cytokine-mediated nitric oxide (NO) production has been shown to be protective in states of oxidative stress. In the absence of oxidative injury, inhibition of NO synthesis has been associated with decreased intracellular levels of reduced glutathione.Methods. To further characterize the role of NO in hepatocyte glutathione...
Background Pulmonary hypertension is a source of perioperative mortality after orthotopic liver transplantation (OLT). The purpose of this study is to (1) characterize the pulmonary hemodynamic response in OLT candidates, and (2) determine whether portal flow index (PFI), a magnetic resonance imaging (MRI)-derived parameter, is a useful predictor of the pulmonary hemodynamic response.Methods. Twenty-five...
Background. Although nitric oxide synthase (NOS) is a cytochrome P450-like hemoprotein with additional sequence homology to cytochrome P450 reductase, the role of the cytochrome P450 system in cytokine-mediated NO synthesis is unknown.Methods. To characterize the role of the P450 system in the synthesis of NO, NO production, NOS enzyme activity, and steady state NOS mRNA and protein expression were...
Background Preoperative assessment of orthotopic liver transplantation candidates requires definition of both the anatomy and metabolic function of the native liver. Current evaluation techniques combine computed tomographic scanning, duplex ultrasonography with blood chemistry analysis, and physical stigmata of end-stage liver disease. Recently, magnetic resonance imaging (MRI) has emerged as an...
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