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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present in vitro and in vivo study we investigated the pro-oxidant effects of hemoglobin, as well as the antioxidant effects of its metabolites, in the brain. Incubation of rat brain homogenates with hemoglobin (0-10 microM) but not hemin induced lipid peroxidation up to 24 h (EC50 = 1.2 microM). Hemoglobin's effects were similar to ferrous ion (EC50 = 1.7 microM) and were blocked by the chelating agent deferoxamine (IC50 0.5 microM) and a nitric oxide-releasing compound S-nitrosoglutathione (IC50 = 40 microM). However, metabolites of hemoglobin - biliverdin and bilirubin - inhibited brain lipid peroxidation induced by cell disruption and hemoglobin (biliverdin IC50 = 12-30 and bilirubin IC50 = 75-170 microM). Biliverdin's antioxidative effects in spontaneous and iron-evoked lipid peroxidation were further augmented by manganese (2 microM) since manganese is an antioxidative transition metal and conjugates with bile pigments. Intrastriatal infusion of hemoglobin (0-24 nmol) produced slight, but significant 20-22% decreases in striatal dopamine levels. Whereas, intrastriatal infusion of ferrous citrate (0-24 nmol) dose-dependently induced a greater 66% depletion of striatal dopamine which was preceded by an acute increase of lipid peroxidation. In conclusion, contrary to the in vitro results hemoglobin is far less neurotoxic than ferrous ions in the brain. It is speculated that hemoglobin may be partially detoxified by heme oxygenase and biliverdin reductase to its antioxidative metabolites in the brain. However, in head trauma and stroke, massive bleeding could significantly produce iron-mediated oxidative stress and neurodegeneration which could be minimized by endogenous antioxidants such as biliverdin, bilirubin, manganese and S-nitrosoglutathione.
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PMID:Hemoglobin and iron-evoked oxidative stress in the brain: protection by bile pigments, manganese and S-nitrosoglutathione. 1063 Jun 86

Reproducible animal models of stroke are indispensable for investigation of pathogenesis and treatment of ischemic brain injury. Defined location and size of infarction as well as consistent production of neurological deficits make it possible to evaluate therapeutic potential of neuroprotective agents as well as to assess the impact of gene deletion [Nat. Med. 3 (1997) 1089; Science 265 (1994) 1883; Nat. Med. 4 (1998) 228] or overexpression [J. Neurochem. 72 (1999) 1187; J. Neurosci. 17 (1997) 7655] on neuroprotection in genetically altered mice. Ischemic stroke in mice can be reliably replicated by means of an open craniectomy exposure followed by permanent occlusion of the trunk and branches of the middle cerebral artery (MCA). Open craniectomy model is known to be statistically robust, yielding a coefficient of variation of <10%, and requiring minimal number of animals to validate the concept of statistical power. In the past, this model as well as some of its variants had been used in pivotal scientific studies to demonstrate impact of therapeutic genes on the course of ischemic neuronal injury [Neuron 13 (1994) 1017], as well as identification of 'culprit genes' responsible for progression of ischemic injury [J. Cerebr. Blood Flow Metab. 14 (1994) 887; Science 265 (1994) 1883; J. Neurosci. 17 (1997) 7655] through continuous recruitment of marginally ischemic penumbra into ischemic core [Trends Neurosci. 22 (1999) 391]. This protocol describes mapping of the ischemic penumbra using NADPH diaphorase staining as well as assessment of penumbral endogenous antioxidant reserves by detection of cellular biliverdin reductase mRNA and protein levels using immunocytochemistry and in situ hybridization histological techniques.
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PMID:Assessment of induction of biliverdin reductase in a mouse model of middle cerebral artery occlusion. 1108 64

Heme oxygenase (HO) is the rate-limiting enzyme in the metabolism of heme-releasing bioactive molecules carbon monoxide (CO), biliverdin, and iron, each with beneficial cardiovascular actions. Biliverdin is rapidly reduced to bilirubin, a potent antioxidant, by the enzyme biliverdin reductase, and iron is rapidly sequestered by ferritin in the cell. Several studies have demonstrated that HO-1 induction can attenuate the development of hypertension as well as lower blood pressure in established hypertension in both genetic and experimental models. HO-1 induction can also reduce target organ injury and can be beneficial in cardiovascular diseases, such as heart attack and stroke. Recent studies have also identified a beneficial role for HO-1 in the regulation of body weight and metabolism in diabetes and obesity. Chronic HO-1 induction lowers body weight and corrects hyperglycemia and hyperinsulinemia. Chronic HO-1 induction also modifies the phenotype of adipocytes in obesity from one of large, cytokine producing to smaller, adiponectin producing. Finally, chronic induction of HO-1 increases oxygen consumption, CO(2), and heat production and activity in obese mice. This review will discuss the current understanding of the actions of the HO system to lower blood pressure and body weight and how HO or its metabolites may be ideal candidates for the development of drugs that can both reduce blood pressure and lower body weight.
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PMID:Heme oxygenase, a novel target for the treatment of hypertension and obesity? 2207 Nov 58

The global epidemic of obesity continues unabated with sequelae of diabetes and metabolic syndrome. This review reflects the dramatic increase in research on the role of increased expression of heme oxygenase (HO)-1/HO-2, biliverdin reductase, and HO activity on vascular disease. The HO system engages with other systems to mitigate the deleterious effects of oxidative stress in obesity and cardiovascular disease (CVD). Recent reports indicate that HO-1/HO-2 protein expression and HO activity have several important roles in hemostasis and reactive oxygen species (ROS)-dependent perturbations associated with metabolic syndrome. HO-1 protects tissue during inflammatory stress in obesity through the degradation of pro-oxidant heme and the production of carbon monoxide (CO) and bilirubin, both of which have anti-inflammatory and anti-apoptotic properties. By contrast, repression of HO-1 is associated with increases of cellular heme and inflammatory conditions including hypertension, stroke, and atherosclerosis. HO-1 is a major focus in the development of potential therapeutic strategies to reverse the clinical complications of obesity and metabolic syndrome.
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PMID:Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome. 2651 32