Expression of the cystine-glutamate exchanger (x(c) (-)) in retinal ganglion cells and regulation by nitric oxide and oxidative stress.
The cystine-glutamate exchanger, system x(c) (-), mediates the Na(+)-independent exchange of cystine into cells, coupled to the efflux of intracellular glutamate. System x(c) (-) plays a critical role in glutathione homeostasis. Early studies of brain suggested that system x(c) (-) was present primarily in astrocytes but not neurons. More recent work indicates that certain brain neurons have an active system x(c) (-). In the retina, system x(c) (-) has been demonstrated in Müller and retinal pigment epithelial cells. We have recently suggested that two protein components of system x(c) (-), xCT and 4F2hc, are present in ganglion cells of the intact retina. Here, we have used (1) molecular and immunohistochemical assays to determine whether system x(c) (-) is present in primary ganglion cells isolated from neonatal mouse retinas and (2) functional assays to determine whether its activity is regulated by oxidative stress in a retinal ganglion cell line (RGC-5). Primary mouse ganglion cells and RGC-5 cells express xCT and 4F2hc. RGC-5 cells take up [(3)H]glutamate in the absence of Na(+), and this uptake is blocked by known substrates of system x(c) (- ) (glutamate, cysteine, cystine, quisqualic acid). Treatment of RGC-5 cells with NO and reactive oxygen species donors leads to increased activity of system x(c) (-) associated with an increase in the maximal velocity of the transporter with no significant change in the substrate affinity. This is the first report of system x(c) (- ) in primary retinal ganglion cells and RGC-5 cells. Oxidative stress upregulates this transport system in RGC-5 cells, and the process is associated with an increase in xCT mRNA and protein but no change in 4F2hc mRNA or protein.[1]References
- Expression of the cystine-glutamate exchanger (x(c) (-)) in retinal ganglion cells and regulation by nitric oxide and oxidative stress. Dun, Y., Mysona, B., Van Ells, T., Amarnath, L., Shamsul Ola, M., Ganapathy, V., Smith, S.B. Cell Tissue Res. (2006) [Pubmed]
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