TY - JOUR
T1 - Oxidative stress and glutathione response in tissue cultures from persons with major depression
AU - Gibson, Sara A.
AU - Korade, Željka
AU - Shelton, Richard C.
N1 - Funding Information:
This research was supported by the Vanderbilt Psychiatric Genotype/Phenotype Project and the Vanderbilt Institute for Clinical and Translational Research ( 1-UL1-RR024975 NCRR/NIH). We would also like to thank the Vanderbilt Kennedy Center and Drs. Beth Ann McLaughlin and Karoly Mirnics for their assistance in this project.
Funding Information:
This work was supported by grant from the Brain & Behavior Research Foundation (NARSAD) and by Vanderbilt Kennedy Center for Research on Human Development .
PY - 2012/10
Y1 - 2012/10
N2 - There is evidence that major depressive disorder (MDD) is associated with increased peripheral markers of oxidative stress. To explore oxidation and antioxidant response in MDD, we assayed human dermal fibroblast cultures derived from skin biopsies of age-, race-, and sex-matched individuals in depressed and normal control groups (n = 16 each group), cultured in glucose and galactose conditions, for relative protein carbonylation (a measure of oxidative stress), glutathione reductase (GR) expression, and total glutathione concentration. In control-group fibroblasts, galactose induced a significant increase from the glucose condition in both protein carbonylation and GR. The cells from the MDD group showed total protein carbonylation and GR expression in the glucose condition that was significantly higher than control cells in glucose and equivalent to controls in galactose. There was a small decrease in protein carbonylation in MDD cells from glucose to galactose and no significant change in GR. There was no difference in total glutathione among any of the groups. Increased protein carbonylation and GR expression, cellular responses to oxidative stress induced by galactose in control fibroblasts, are present in fibroblasts derived from MDD patients and are not explainable by reduced GR or total glutathione in the depressed patients. These studies support the role of oxidative stress in the pathophysiology of MDD. Further confirmation of these findings could lead to the development of novel antioxidant approaches for the treatment of depression.
AB - There is evidence that major depressive disorder (MDD) is associated with increased peripheral markers of oxidative stress. To explore oxidation and antioxidant response in MDD, we assayed human dermal fibroblast cultures derived from skin biopsies of age-, race-, and sex-matched individuals in depressed and normal control groups (n = 16 each group), cultured in glucose and galactose conditions, for relative protein carbonylation (a measure of oxidative stress), glutathione reductase (GR) expression, and total glutathione concentration. In control-group fibroblasts, galactose induced a significant increase from the glucose condition in both protein carbonylation and GR. The cells from the MDD group showed total protein carbonylation and GR expression in the glucose condition that was significantly higher than control cells in glucose and equivalent to controls in galactose. There was a small decrease in protein carbonylation in MDD cells from glucose to galactose and no significant change in GR. There was no difference in total glutathione among any of the groups. Increased protein carbonylation and GR expression, cellular responses to oxidative stress induced by galactose in control fibroblasts, are present in fibroblasts derived from MDD patients and are not explainable by reduced GR or total glutathione in the depressed patients. These studies support the role of oxidative stress in the pathophysiology of MDD. Further confirmation of these findings could lead to the development of novel antioxidant approaches for the treatment of depression.
KW - Glutathione
KW - Glutathione reductase
KW - Human dermal fibroblasts
KW - Major depression
KW - Oxidative stress
KW - Protein carbonylation
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U2 - 10.1016/j.jpsychires.2012.06.008
DO - 10.1016/j.jpsychires.2012.06.008
M3 - Article
C2 - 22841833
AN - SCOPUS:84865560008
SN - 0022-3956
VL - 46
SP - 1326
EP - 1332
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
IS - 10
ER -