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: Glutathione depletion causes a JNK and p38MAPK-mediated increase in expression of cystathionine-gamma-lyase and upregulation of the transsulfuration pathway in C6 glioma cells.
    Author: Kandil S, Brennan L, McBean GJ.
    Journal: Neurochem Int; 2010 Mar; 56(4):611-9. PubMed ID: 20060865.
    Abstract:
    Cancer cells have a high demand for cysteine as precursor of the antioxidant, glutathione, that is required to promote cell growth and division. Uptake of cystine by the x(c)(-) cystine-glutamate exchanger provides the majority of cysteine, but a significant percentage may be derived from methionine, via a transsulfuration pathway. Our aim was to evaluate the relative contribution of the exchanger and the transsulfuration pathway to glutathione synthesis in astrocytoma/glioblastoma cells, using the C6 glioma cell line as a model system. Blockade of the x(c)(-) exchanger with the gliotoxins l-alphaaminoadipate or l-beta-N-oxalylamino-l-alanine (400 microM) caused a loss of cellular cysteine and depletion in glutathione to 51% and 54% of control, respectively, after 24 h. Inhibition of the transsulfuration pathway with propargylglycine (1 mM, 24 h) depleted glutathione to 77% of control. Co-incubation of cells with gliotoxin and propargylglycine reduced glutathione to 39% of control at 24 h and to 20% at 48 h. Expression of cystathionine-gamma-lyase, the rate-limiting enzyme of the transsulfuration pathway, was significantly increased following incubation of the cells with gliotoxins. Incubation of C6 cells with diethylmaleate for 3 h led to a significant reduction in glutathione (63%), whereas expression of cystathionine-gamma-lyase was increased by 1.5-fold. Re-feeding methionine to diethylmaleate-treated cells incubated in the absence of cystine or methionine resulted in a significant recovery in glutathione that was blocked by propargylglycine. Co-incubation of C6 cells with diethylmaleate and the JNK-inhibitor, SP600125, abolished the increase in expression of cystathionine-gamma-lyase that had been observed in the presence of diethylmaleate alone. Similar results were obtained with the p38(MAPK) inhibitor, SB203580. It is concluded that glutathione depletion causes a JNK- and p38(MAPK)-mediated increase in expression of cystathionine-gamma-lyase that promotes flux through the transsulfuration pathway to compensate for loss of glutathione in C6 glioma cells.
    [Abstract] [Full Text] [Related] [New Search]