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
Files in This Item:
|Kandil_et_al_2010_Neurochem_Int_56_611-619.pdf||784.85 kB||Adobe PDF||Download|
|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||Authors:||Kandil, Sarah
McBean, Gethin J.
|Permanent link:||http://hdl.handle.net/10197/6620||Date:||Mar-2010||Online since:||2015-06-22T11:15:56Z||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 View the MathML source 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 View the MathML source exchanger with the gliotoxins l-αaminoadipate or l-β-N-oxalylamino-l-alanine (400 μM) 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-γ-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-γ-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-γ-lyase that had been observed in the presence of diethylmaleate alone. Similar results were obtained with the p38MAPK inhibitor, SB203580. It is concluded that glutathione depletion causes a JNK- and p38MAPK-mediated increase in expression of cystathionine-γ-lyase that promotes flux through the transsulfuration pathway to compensate for loss of glutathione in C6 glioma cells.||Funding Details:||Science Foundation Ireland||Type of material:||Journal Article||Publisher:||Elsevier||Journal:||Neurochemistry International||Volume:||56||Issue:||4||Start page:||611||End page:||619||Copyright (published version):||2010 Elsevier||Keywords:||Cystine-glutamate exchanger; Gliotoxin; Astrocyte; Transulfuration; C6 glioma; Cystathionine-g-lyase; Glutathione||DOI:||10.1016/j.neuint.2010.01.004||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Biomolecular and Biomedical Science Research Collection|
Agriculture and Food Science Research Collection
Show full item record
Page view(s) 5051
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.