TY - JOUR
T1 - Serum deprivation inhibits glutathione depletion-induced death in embryonic cortical neurons
T2 - Evidence against oxidative stress as a final common mediator of neuronal apoptosis
AU - Ratan, Rajiv R.
AU - Lee Paul, J.
AU - Baraban, Jay M.
N1 - Funding Information:
This work was supported by an NRSA Neurorehabilitation Fellowship Institutional Training Grant 5T32HD07428 (R.R.R.) and a Passano Foundation Clinician Scientist Award (R.R.R.).
PY - 1996/8
Y1 - 1996/8
N2 - We have previously shown that glutamate-induced cystine deprivation of embryonic cortical neurons leads to intracellular depletion of the antioxidant glutathione, consequent oxidative stress and apoptotic cell death. To test the hypothesis that glutathione depletion and oxidative stress represent a common pathway of neuronal apoptosis, we examined the effect of a variety of antioxidants on serum deprivation-induced death in embryonic cortical neurons. A host of antioxidant agents, capable of abrogating glutathione depletion-induced apoptosis in cortical neurons, were unable to inhibit serum deprivation-induced death in these cells. To test whether serum deprivation and glutathione depletion involve different or antagonistic pathways, we serum-deprived cortical neurons at the time of induction of glutathione depletion. Surprisingly, we found that serum deprivation diminished glutathione depletion-induced death as compared to cultures treated with growth factors or serum. These observations suggest that serum deprivation antagonizes the cell death signaling pathway activated by glutathione depletion and that serum and growth factors can enhance susceptibility to oxidative stress. Consistent with these conclusions, we show that growth factors or serum added in combination with antioxidants possess superior survival promoting effects as compared to either agent alone.
AB - We have previously shown that glutamate-induced cystine deprivation of embryonic cortical neurons leads to intracellular depletion of the antioxidant glutathione, consequent oxidative stress and apoptotic cell death. To test the hypothesis that glutathione depletion and oxidative stress represent a common pathway of neuronal apoptosis, we examined the effect of a variety of antioxidants on serum deprivation-induced death in embryonic cortical neurons. A host of antioxidant agents, capable of abrogating glutathione depletion-induced apoptosis in cortical neurons, were unable to inhibit serum deprivation-induced death in these cells. To test whether serum deprivation and glutathione depletion involve different or antagonistic pathways, we serum-deprived cortical neurons at the time of induction of glutathione depletion. Surprisingly, we found that serum deprivation diminished glutathione depletion-induced death as compared to cultures treated with growth factors or serum. These observations suggest that serum deprivation antagonizes the cell death signaling pathway activated by glutathione depletion and that serum and growth factors can enhance susceptibility to oxidative stress. Consistent with these conclusions, we show that growth factors or serum added in combination with antioxidants possess superior survival promoting effects as compared to either agent alone.
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U2 - 10.1016/0197-0186(95)00115-8
DO - 10.1016/0197-0186(95)00115-8
M3 - Article
C2 - 8837044
AN - SCOPUS:0030222320
SN - 0197-0186
VL - 29
SP - 153
EP - 157
JO - Neurochemistry International
JF - Neurochemistry International
IS - 2
ER -