Stephen Cherne

Project title: Signaling Events Involved in the Inductible Expression of Nitric Oxide Synthase in Rat Kidney Cells

Degree: MS (Thesis) | Program: Environmental Toxicology (Tox) | Project type: Thesis/Dissertation
Completed in: 2002 | Faculty advisor: James S. Woods


Nitric Oxide is a free radical produced by an oxidation of the guanidino group of L-arginine catalyzed by Nitric Oxide Synthase (NOS). There are three isofoRMS of NOS and are widely distributed in many tissue types. Neuronal NOS (nNOS) and endothelial NOS (eNOS) are both constitutively expressed at low levels, while inducible NOS (iNOS) is not expressed until it is transcriptionally induced by endogenous and/or exogenous stimuli. However, when iNOS is up regulated, the resulting nitric oxide level produced is generally higher in concentration and of a longer duration compared to nitric oxide levels produced by the other two isoforms. Nitric oxide has multiple physiological roles depending on the NOS isoform and tissue in which it is being produced (1). Nitric oxide acts as a neurotransmitter when produced by nNOS, which is expressed in both the peripheral and central nervous tissue. Nitric oxide is also a potent regulator of vasodilation when produced by eNOS, which is expressed in many tissues including the endothelial cells lining blood vessels. The inducible form of NOS (iNOS) is highly inducible in macrophages, as well as other tissues including the kidney proximal epithelial cells, and is utilized during immune and inflammatory responses due to the antimicrobial and antiviral properties of nitric oxide (2). In addition to the up regulation of iNOS in macrophages following stimulation with an exogenous stimuli, such as the bacterial endotoxin, lipopolysaccharide (LPS), cytokine production is also increased in these cells. Cytokines such as gamma interferon (IFN-g) also contribute to an increased level of iNOS transcription (3,4).

Taken from the beginning of thesis.