PMID: 7521125Aug 11, 1994Paper

Hepatocyte inducible nitric oxide synthesis is influenced in vitro by cell density

The American Journal of Physiology
A K NüsslerR L Simmons

Abstract

Hepatocyte plating density is known to affect cell function. Human and rat hepatocytes have been shown to express the inducible nitric oxide synthase (INOS) in response to cytokines plus lipopolysaccharide (LPS). The following studies were performed to determine the effects of hepatocyte plating density on the regulation of INOS. Rat hepatocytes were plated at densities from 10(4) to 20 x 10(4) hepatocytes/cm2 and stimulated with a combination of LPS, interferon-gamma, interleukin-1, and tumor necrosis factor. We found that NO2- plus NO3- released from stimulated hepatocytes declines with increasing hepatocyte density. Similar effects were seen for 3',5'-cyclic monophosphate release into supernatants and in the amount of nonheme iron-nitrosyl signals measured by electron paramagnetic resonance spectroscopy. Limitations of substrate (L-arginine) and 5,6,7,8-tetrahydrobiopterin were excluded as cause of the reduced nitric oxide generation at higher densities. Although mRNA levels for INOS were not influenced when measured at 24 h, there was a marked reduction in INOS enzyme activity and INOS protein detectable by Western blotting at higher cell density. Total protein synthesis decreased as hepatocyte density increased in both non...Continue Reading

Citations

Sep 9, 1999·In Vitro Cellular & Developmental Biology. Animal·A K NusslerS C Strom
Jul 30, 2005·World Journal of Gastroenterology : WJG·Lie-Gang LiuXiu-Fa Sun
Jan 22, 2014·Cytotechnology·Xiaobing GongPeter Neuhaus
Nov 20, 2003·Shock·Ulrich C LienerFlorian Gebhard
Mar 28, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ping YaoAndreas Nussler
Apr 27, 2000·Journal of Hepatology·C VargiuS Colombatto
Aug 5, 2003·Nitric Oxide : Biology and Chemistry·Aaron T Jacobs, Louis J Ignarro
Jan 1, 1995·Advances in Neuroimmunology·H SuzukiU Armato
Dec 17, 2005·Toxicology Letters·Masashi ShimadaAndreas K Nussler

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