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- _5 label "Selventa" provenance.
- large_corpus.bel rights "Copyright (c) 2011-2012, Selventa. All rights reserved." provenance.
- _4 value "Stroke is one of the leading causes of death in major industrial countries. Many factors contribute to the cellular damage resulting from ischemia/reperfusion (I/R). Experimental data indicate an important role for oxidative stress and the inflammatory cascade during I/R. We are testing the hypothesis that the mechanism of protection against I/R damage observed in transgenic mice overexpressing human antioxidant enzymes (particularly intracellular glutathione peroxidase) involves the modulation of inflammatory response as well as reduced sensitivity of neurons to cytotoxic cytokines. Transgenic animals show significant reduction of expression of chemokines, IL-6, and cell death-inducing ligands as well as corresponding receptors in a focal cerebral I/R model. Reduction of DNA binding activity of consensus and potential AP-1 binding sites in mouse Fas ligand promoter sequence was observed in nuclear extracts from transgenic mice overexpressing intracellular glutathione peroxidase compared with normal animals following I/R. This effect was accompanied by modulation of the c-Jun N-terminal kinase/stress-activated protein kinase pathway. Cultured primary neurons from the transgenic mice demonstrated protection against hypoxia/reoxygenation injury as well as cytotoxicity after TNF-alpha and Fas ligand treatment. These results indicate that glutathione peroxidase-sensitive reactive oxygen species play an important role in regulation of cell death during cerebral I/R by modulating intrinsic neuronal sensitivity as well as brain inflammatory reactions." provenance.
- _4 wasQuotedFrom 11823528 provenance.
- assertion hadPrimarySource 11823528 provenance.
- large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
- large_corpus.bel description "Approximately 61,000 statements." provenance.
- assertion wasDerivedFrom _4 provenance.
- assertion wasDerivedFrom large_corpus.bel provenance.
- large_corpus.bel authoredBy _5 provenance.
- large_corpus.bel version "20131211" provenance.