Glutathione peroxidase inhibits cell death and glial activation following experimental stroke.
Stroke is a leading cause of morbidity and mortality in major industrial countries. Many factors contribute to the cellular damage resulting from ischemia-reperfusion (I-R). Growing evidence indicates that reactive oxygen species (ROS) contribute significantly to this process, though their exact mechanism of action is mostly unknown. We have examined the mechanism of protection against I-R injury in transgenic mice that overexpress human glutathione peroxidase (hGPx1), using a focal cerebral I-R model. In this model, transgenic animals show significant reduction of necrotic as well as apoptotic cell death in vulnerable brain regions as demonstrated by TUNEL staining, DNA laddering and ELISA assays. We also observed decreased astrocytic and microglial activation in ischemic brains of animals overexpressing hGPx1. In wild-type mice, neuronal cell death was accompanied with compromise of vascular integrity, edema and neutrophil infiltration, whereas GPx1 mice revealed significant preservation of tissue structure and decreased infiltration of acute inflammatory cells. These results indicate that glutathione peroxidase-sensitive ROS play an important role in regulation of cell death during cerebral I-R as well as in brain inflammatory reactions.
Ishibashi
Nobuya
N
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Prokopenko
Olga
O
Weisbrot-Lefkowitz
Miriam
M
Reuhl
Kenneth R
KR
Mirochnitchenko
Oleg
O
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000502:physiology*; D002465:Cell Movement; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury; D020521:Stroke / Q000503:physiopathology*; D000094765:Glutathione Peroxidase GPX1
D005904:Glial Fibrillary Acidic Protein; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1