title: Targeting antioxidant enzyme expression as a therapeutic strategy for ischemic stroke.
abstract: During ischemic stroke, neurons and glia are subjected to damage during the acute and neuroinflammatory phases of injury. Production of reactive oxygen species (ROS) from calcium dysregulation in neural cells and the invasion of activated immune cells are responsible for stroke-induced neurodegeneration. Scientists have failed thus far to identify antioxidant-based drugs that can enhance neural cell survival and improve recovery after stroke. However, several groups have demonstrated success in protecting against stroke by increasing expression of antioxidant enzymes in neural cells. These enzymes, which include but are not limited to enzymes in the glutathione peroxidase, catalase, and superoxide dismutase families, degrade ROS that otherwise damage cellular components such as DNA, proteins, and lipids. Several groups have identified cellular therapies including neural stem cells and human umbilical cord blood cells, which exert neuroprotective and oligoprotective effects through the release of pro-survival factors that activate PI3K/Akt signaling to upregulation of antioxidant enzymes. Other studies demonstrate that treatment with soluble factors released by these cells yield similar changes in enzyme expression after stroke. Treatment with the cytokine leukemia inhibitory factor increases the expression of peroxiredoxin IV and metallothionein III in glia and boosts expression of superoxide dismutase 3 in neurons. Through cell-specific upregulation of these enzymes, LIF and other Akt-inducing factors have the potential to protect multiple cell types against damage from ROS during the early and late phases of ischemic damage.
authors.affiliation: Center for Advanced Translational Stroke Science, Depts of Neurology and Anatomy & Neurobiology, University of Kentucky, 741 S. Limestone Ave., BBSRB B457, Lexington, KY 40536-0509, United States.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Davis
authors.affiliation: Center for Advanced Translational Stroke Science, Depts of Neurology and Anatomy & Neurobiology, University of Kentucky, 741 S. Limestone Ave., BBSRB B457, Lexington, KY 40536-0509, United States. Electronic address: keith.pennypacker@uky.edu.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Pennypacker
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016503:Drug Delivery Systems / Q000639:trends; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase; C441642:SOD3 protein, human; D013482:Superoxide Dismutase
keywords: Antioxidant enzymes; Ischemic stroke; Leukemia inhibitory factor; Neuroprotection; Oxidative stress