Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat.
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.
Department of Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Mary Latha
ML
Rathinam
Lora Talley
LT
Watts
Madhusudhanan
M
Narasimhan
Amanjot Kaur
AK
Riar
Lenin
L
Mahimainathan
George I
GI
Henderson
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D018920:Coculture Techniques; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D006540:Herbicides; D007306:Insecticides; D017382:Reactive Oxygen Species; D012402:Rotenone; D005723:gamma-Glutamyltransferase; D018826:CD13 Antigens; D005978:Glutathione; D010269:Paraquat