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PMID:11579147

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Citation

Crack, PJ, Taylor, JM, Flentjar, NJ, de Haan, J, Hertzog, P, Iannello, RC and Kola, I (2001) Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury. J. Neurochem. 78:1389-99

Abstract

Glutathione peroxidase is an antioxidant enzyme that is involved in the control of cellular oxidative state. Recently, unregulated oxidative state has been implicated as detrimental to neural cell viability and involved in both acute and chronic neurodegeneration. In this study we have addressed the importance of a functional glutathione peroxidase in a mouse ischemia/reperfusion model. Two hours of focal cerebral ischemia followed by 24 h of reperfusion was induced via the intraluminal suture method. Infarct volume was increased three-fold in the glutathione peroxidase-1 (Gpx-1) -/- mouse compared with the wild-type mouse; this was mirrored by an increase in the level of apoptosis found at 24 h in the Gpx-1 -/- mouse compared with the wild-type mouse. Neuronal deficit scores correlated to the histologic data. We also found that activated caspase-3 expression is present at an earlier time point in the Gpx-1 -/- mice when compared with the wild-type mice, which suggests an enhanced susceptibility to apoptosis in the Gpx-1 -/- mouse. This is the first known report of such a dramatic increase, both temporally and in level of apoptosis in a mouse stroke model. Our results suggest that Gpx-1 plays an important regulatory role in the protection of neural cells in response to the extreme oxidative stress that is released during ischemia/reperfusion injury.

Links

PubMed

Keywords

Animals; Apoptosis; Brain/pathology; Brain/physiopathology; Brain Ischemia/pathology; Brain Ischemia/physiopathology; Caspase 3; Caspases/metabolism; Cerebral Infarction/pathology; Cerebral Infarction/physiopathology; Enzyme Activation/physiology; Glutathione Peroxidase/genetics; Glutathione Peroxidase/physiology; Lipid Peroxides/metabolism; Mice; Mice, Knockout/genetics; Neurons/physiology; Reperfusion Injury/pathology; Reperfusion Injury/physiopathology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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