Peroxisome proliferator-activated receptor-gamma agonists promote differentiation and antioxidant defenses of oligodendrocyte progenitor cells.
Several lines of evidence suggest that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists may control brain inflammation and, therefore, may be useful for the treatment of human CNS inflammatory conditions. The PPAR-gamma agonists delay the onset and ameliorate clinical manifestations in animal demyelinating disease models, in which the beneficial effects are thought to be mainly related to anti-inflammatory effects on peripheral and brain immune cells. Direct effects on neurons, oligodendrocytes, and other CNS resident cells cannot be excluded, however. To analyze potential direct actions of PPAR-gamma agonists on oligodendrocytes, we investigated the effects of both natural (15-deoxy Delta prostaglandin J2) and synthetic (pioglitazone) PPAR-gamma agonists in primary cultures of rat oligodendrocyte progenitor cells. The PPAR-gamma agonists promoted oligodendrocyte progenitor cell differentiation and enhanced their antioxidant defenses by increasing levels of catalase and copper-zinc superoxide dismutase while maintaining the overall homeostasis of the glutathione system. Protective effects were abolished in the presence of the specific PPAR-gamma antagonist GW9662, indicating that they are specifically dependent on PPAR-gamma. These observations suggest that in addition to their known anti-inflammatory effects, PPAR-gamma agonists may protect oligodendrocyte progenitor cells by preserving their integrity and favoring their differentiation into myelin-forming cells. Thus, PPAR-gamma may promote recovery from demyelination by direct effects on oligodendrocytes.
Bernardo
Antonietta
A
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
Bianchi
Daniela
D
Magnaghi
Valerio
V
Minghetti
Luisa
L
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000975:Antioxidants; D047495:PPAR gamma; D045162:Thiazolidinediones; D002374:Catalase; D013482:Superoxide Dismutase; D015230:Prostaglandin D2; D000077205:Pioglitazone