Project Details
Description
One of the fundamental actions of pro-inflammatory mediators is the induction of the enzyme nitric oxide synthase (iNOS) both in vivo and in a variety of cell types in vitro.
The overproduction of nitric oxide (NO) by iNOS has been implicated as the major cause of some of the deleterious effects in vascular inflammatory diseases such as septic and cytokine-induced circulatory shock.
Studies carried out in our laboratory have shown that uptake of L-arginine via the cationic amino acid transporters (CATs) is increased in cultured cells generating NO, and further established that sustained production of NO under these conditions is critically dependent on the transport of extracellular L-arginine.
These findings suggest that increase in CAT activity may play a critical role in NO formation and regulation of these proteins, in parallel with iNOS, provides a potential therapeutic opportunity for limiting NO production in diseases arising from NO excess.
Our research is therefore focused on obtaining a clear understanding of the regulation of expression and function of the inducible L-arginine-NO pathway in cultured vascular cells using both Pharmacological and molecular approaches. Ongoing studies are aimed at determining the:
>Relationship between CAT expression and function and NO synthesis
>Molecular nature and regulation of expression and function of CATs
>Transport mechanisms for nitric oxide synthase inhibitors
signalling for iNOS and/or CATs induction
>Regulation of the inducible L-arginine-NO pathway by statins
The overproduction of nitric oxide (NO) by iNOS has been implicated as the major cause of some of the deleterious effects in vascular inflammatory diseases such as septic and cytokine-induced circulatory shock.
Studies carried out in our laboratory have shown that uptake of L-arginine via the cationic amino acid transporters (CATs) is increased in cultured cells generating NO, and further established that sustained production of NO under these conditions is critically dependent on the transport of extracellular L-arginine.
These findings suggest that increase in CAT activity may play a critical role in NO formation and regulation of these proteins, in parallel with iNOS, provides a potential therapeutic opportunity for limiting NO production in diseases arising from NO excess.
Our research is therefore focused on obtaining a clear understanding of the regulation of expression and function of the inducible L-arginine-NO pathway in cultured vascular cells using both Pharmacological and molecular approaches. Ongoing studies are aimed at determining the:
>Relationship between CAT expression and function and NO synthesis
>Molecular nature and regulation of expression and function of CATs
>Transport mechanisms for nitric oxide synthase inhibitors
signalling for iNOS and/or CATs induction
>Regulation of the inducible L-arginine-NO pathway by statins
Status | Active |
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Effective start/end date | 1/01/13 → … |
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