These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Adaptive responses to peroxynitrite: increased glutathione levels and cystine uptake in vascular cells.
    Author: Buckley BJ, Whorton AR.
    Journal: Am J Physiol Cell Physiol; 2000 Oct; 279(4):C1168-76. PubMed ID: 11003597.
    Abstract:
    We and others recently demonstrated increased glutathione levels, stimulated cystine uptake, and induced gamma-glutamylcysteinyl synthase (gamma-GCS) in vascular cells exposed to nitric oxide donors. Here we report the effects of peroxynitrite on glutathione levels and cystine uptake. Treatment of bovine aortic endothelial and smooth muscle cells with 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, resulted in transient depletion of glutathione followed by a prolonged increase beginning at 8-9 h. Concentration-dependent increases in glutathione of up to sixfold occurred 16-18 h after 0.05-2.5 mM SIN-1. Responses to SIN-1 were inhibited by copper-zinc superoxide dismutases and manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride, providing evidence for peroxynitrite involvement. Because glutathione synthesis is regulated by amino acid availability, we also studied cystine uptake. SIN-1 treatment resulted in a prolonged increase in cystine uptake beginning at 6-9 h. Increases in cystine uptake after SIN-1 were blocked by inhibitors of protein and RNA synthesis, by extracellular glutamate but not by extracellular sodium. These studies suggest induction of the x(c)(-) pathway of amino acid uptake. A close correlation over time was observed for increases in cystine uptake and glutathione levels. In summary, vascular cells respond to chronic peroxynitrite exposure with adaptive increases in cellular glutathione and cystine transport.
    [Abstract] [Full Text] [Related] [New Search]