Peroxisomal localization of inducible nitric oxide synthase in hepatocytes.

Abstract	Shock states induce the expression of inducible nitric oxide synthase (iNOS) in both Kupffer cells and hepatocytes in the liver, but little is known about its subcellular localization in these cells. Studies were undertaken to characterize the subcellular location of iNOS in hepatocytes in response to sepsis. By immunofluorescence analysis, intraperitoneal challenge with bacterial lipopolysaccharide induced cytosolic iNOS in Kupffer cells but punctate labeling in hepatocytes. Cultured rat hepatocytes exposed to interferon gamma, interleukin 1, and tumor necrosis factor alpha showed iNOS protein expression within peroxisomes as early as 4 hours after stimulation, as determined by colabeling for catalase or PMP70. To a lesser extent, iNOS was also observed associated with the plasma membrane and in undefined intracellular aggregates. The nitric oxide synthase (NOS) antagonist L-N-imino-ornithine (L-NIO) did not affect the expression of iNOS within peroxisomes, cytoplasmic aggregates, or cytosol but increased plasma membrane localization of iNOS. Human iNOS transduced into iNOS-null mouse hepatocytes using an adenoviral vector also localized to peroxisomes. The expression of iNOS often resulted in the disappearance of detectable catalase in many hepatocytes. In conclusion, these studies establish the peroxisome as a site of iNOS localization in hepatocytes and show a relationship between iNOS up-regulation and decreased expression of catalase.
Authors	Donna Beer Stolz, Ruben Zamora, Yoram Vodovotz, Patricia A Loughran, Timothy R Billiar, Young-Myeong Kim, Richard L Simmons, Simon C Watkins
Journal	Hepatology (Baltimore, Md.) (Hepatology) Vol. 36 Issue 1 Pg. 81-93 (Jul 2002) ISSN: 0270-9139 [Print] United States
PMID	12085352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	ABCD3 protein, human ATP-Binding Cassette Transporters Abcd3 protein, mouse Abcd3 protein, rat Cytokines DNA Probes Interleukin-1 Lipopolysaccharides Membrane Proteins Tumor Necrosis Factor-alpha Interferon-gamma Catalase NOS2 protein, human Nitric Oxide Synthase Nitric Oxide Synthase Type II Nos2 protein, mouse Nos2 protein, rat
Topics	ATP-Binding Cassette Transporters Animals Blotting, Northern Blotting, Western Catalase (genetics) Cells, Cultured Cytokines (pharmacology) DNA Probes Fluorescent Antibody Technique Hepatocytes (enzymology, ultrastructure) Humans Interferon-gamma (pharmacology) Interleukin-1 (pharmacology) Kupffer Cells (enzymology) Lipopolysaccharides (pharmacology) Male Membrane Proteins (analysis) Mice Mice, Knockout Microscopy, Confocal Microscopy, Electron Microscopy, Fluorescence Nitric Oxide Synthase (analysis, deficiency, genetics) Nitric Oxide Synthase Type II Peroxisomes (enzymology) Rats Rats, Sprague-Dawley Transfection Tumor Necrosis Factor-alpha (pharmacology)

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