TY - JOUR
T1 - Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat
AU - Rathinam, Mary Latha
AU - Watts, Lora Talley
AU - Narasimhan, Madhusudhanan
AU - Riar, Amanjot Kaur
AU - Mahimainathan, Lenin
AU - Henderson, George I.
PY - 2012/3
Y1 - 2012/3
N2 - Primary cultures of fetal rat cortical neurons and astrocytes were used to test the hypothesis that astrocyte-mediated control of neuronal glutathione (GSH) is a potent factor in neuroprotection against rotenone and paraquat. In neurons, rotenone (0.025-1 μM) for 4 and 24. h decreased viability as did paraquat (2-100 μM). Rotenone (30. nM) decreased neuronal viability and GSH by 24% and 30%, while ROS were increased by 56%. Paraquat (30 μM) decreased neuronal viability and GSH by 36% and 70%, while ROS were increased by 23%. When neurons were co-cultured with astrocytes, their GSH increased 1.5 fold and 5 fold at 12 and 24. h. Co-culturing with astrocytes blocked neuronal death and damage by rotenone and paraquat. Astrocyte-mediated neuroprotection was dependent on the activity of components of the γ-glutamyl cycle. These studies illustrate the importance of astrocyte-mediated glutathione homeostasis for protection of neurons from rotenone and paraquat and the role of the γ-glutamyl cycle in this neuroprotection.
AB - Primary cultures of fetal rat cortical neurons and astrocytes were used to test the hypothesis that astrocyte-mediated control of neuronal glutathione (GSH) is a potent factor in neuroprotection against rotenone and paraquat. In neurons, rotenone (0.025-1 μM) for 4 and 24. h decreased viability as did paraquat (2-100 μM). Rotenone (30. nM) decreased neuronal viability and GSH by 24% and 30%, while ROS were increased by 56%. Paraquat (30 μM) decreased neuronal viability and GSH by 36% and 70%, while ROS were increased by 23%. When neurons were co-cultured with astrocytes, their GSH increased 1.5 fold and 5 fold at 12 and 24. h. Co-culturing with astrocytes blocked neuronal death and damage by rotenone and paraquat. Astrocyte-mediated neuroprotection was dependent on the activity of components of the γ-glutamyl cycle. These studies illustrate the importance of astrocyte-mediated glutathione homeostasis for protection of neurons from rotenone and paraquat and the role of the γ-glutamyl cycle in this neuroprotection.
KW - Astrocytes
KW - Glutathione
KW - Neurons
KW - Paraquat
KW - Rotenone
KW - γ-Glutamyl cycle
UR - http://www.scopus.com/inward/record.url?scp=84856327256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856327256&partnerID=8YFLogxK
U2 - 10.1016/j.etap.2011.12.027
DO - 10.1016/j.etap.2011.12.027
M3 - Article
C2 - 22301167
AN - SCOPUS:84856327256
VL - 33
SP - 353
EP - 360
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
SN - 1382-6689
IS - 2
ER -