Linked Life Data

10037492

Source:http://linkedlifedata.com/resource/pubmed/id/10037492

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-3-18
pubmed:abstractText
Heme oxygenase-1 (HO-1, HSP32) is an early gene that is responsive to an array of pathological conditions including, but not limited to, hypoxia and cerebral ischemia. HO-1 cleaves the heme molecule and produces carbon monoxide (CO) and biliverdin (an antioxidant) and is essential for iron homeostasis. The purpose of this study was to investigate, using transgenic (Tg) mice, whether overexpression of HO-1 in the brain augments or attenuates cellular injury caused by ischemic stroke. Homozygous HO-1 Tg mice that overexpress HO-1 under the control of the neuron-specific enolase promoter (characterized previously) were used. Under halothane anesthesia and normothermic conditions, wild-type nontransgenic (nTg; n = 22) and HO-1 Tg (n = 24) mice were subjected to middle cerebral artery occlusion (MCAo). Six hours after induction of ischemia, Tg and nTg mice developed infarcts that were 39 +/- 6 and 63 +/- 9 mm3, respectively (p < 0.01). No significant difference between the two strains was observed in the values of brain edema (11.3 +/- 4% in Tg vs. 14.6 +/- 5% in nTg; p < 0.1). At 24 h after MCAo, Tg mice exhibited significant neuroprotection as determined by the stroke volumes (41 +/- 2 mm3 in Tg vs. 74 +/- 5 mm3 in nTg; p < 0.01) and values of ischemic cerebral edema (21 +/- 6% in Tg vs. 35 +/- 11% in nTg; p < 0.01). Data suggest that neuroprotection in Tg mice was, at least in part, related to the following findings: (a) constitutively up-regulated cyclic GMP and bcl-2 levels in neurons; (b) inhibition of nuclear localization of p53 protein; and (c) antioxidant action of HO-1, as detected by postischemic neuronal expression of ferritin, and decreases in iron staining and tissue lipid peroxidation. We suggest that pharmacological stimulation of HO-1 activity may constitute a novel therapeutic approach in the amelioration of ischemic injury during the acute period of stroke.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1187-203
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10037492-Animals, pubmed-meshheading:10037492-Arterial Occlusive Diseases, pubmed-meshheading:10037492-Behavior, Animal, pubmed-meshheading:10037492-Blotting, Northern, pubmed-meshheading:10037492-Brain Edema, pubmed-meshheading:10037492-Brain Ischemia, pubmed-meshheading:10037492-Cerebral Arterial Diseases, pubmed-meshheading:10037492-Cerebrovascular Circulation, pubmed-meshheading:10037492-Cyclic GMP, pubmed-meshheading:10037492-Ferritins, pubmed-meshheading:10037492-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10037492-Heme Oxygenase (Decyclizing), pubmed-meshheading:10037492-Heme Oxygenase-1, pubmed-meshheading:10037492-Immunohistochemistry, pubmed-meshheading:10037492-Lipid Peroxidation, pubmed-meshheading:10037492-Membrane Proteins, pubmed-meshheading:10037492-Mice, pubmed-meshheading:10037492-Mice, Transgenic, pubmed-meshheading:10037492-NADPH Dehydrogenase, pubmed-meshheading:10037492-Neurons, pubmed-meshheading:10037492-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:10037492-Stroke Volume, pubmed-meshheading:10037492-Tumor Suppressor Protein p53
pubmed:year
1999
pubmed:articleTitle
Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice.
pubmed:affiliation
Department of Biochemistry and Biophysics, University of Rochester School of Medicine, New York 14642, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't