Abstract
Cerebral ischemia is the third leading cause of death in industrialized countries and an important health system problem with no efficient treatment to date. The reduction in oxygen and glucose supply triggers a cascade of events such as excitotoxicity, oxidative stress, inflammation, apoptosis, and an adjustment of the gene expression program. The hypoxia inducible factor-1 (HIF-1) is a transcription factor that mediates the adaptive responses to the reduction in oxygen availability. HIF-1 activation in hypoxic conditions promotes the survival of cells through the induction of adaptive genes involved in glucose and energy production, glucose transport, cell proliferation, cell survival, iron homeostasis, erythropoiesis, angiogenesis and vascular reactivity. In recent years, biomedical research has focused on the oxygen regulated α subunit of HIF-1 as a potential therapy in medical events that involve hypoxic conditions. In this review we summarize current knowledge on the use of HIF-1α as a therapeutic target against cerebral ischemia through two different strategies: 1) the use of ischemic preconditioning to induce the HIF-1 pathway regulation, and 2) the pharmacological inhibition of prolyl and asparaginyl hydroxylases. Both strategies appear as attractive options for protection in ischemia in which signaling pathway activation could contribute to the establishment of tolerance in brain.
Keywords: Hypoxia inducible factor, ischemic preconditioning, prolyl hydroxylase, cerebral ischemia
Current Signal Transduction Therapy
Title: Hypoxia Inducible Factor-1 as a Therapeutic Target in Cerebral Ischemia
Volume: 4 Issue: 3
Author(s): Penelope Aguilera, Edgar Vazquez-Contreras, Carlos Daniel Gomez-Martínez and Maria Elena Chanez Cardenas
Affiliation:
Keywords: Hypoxia inducible factor, ischemic preconditioning, prolyl hydroxylase, cerebral ischemia
Abstract: Cerebral ischemia is the third leading cause of death in industrialized countries and an important health system problem with no efficient treatment to date. The reduction in oxygen and glucose supply triggers a cascade of events such as excitotoxicity, oxidative stress, inflammation, apoptosis, and an adjustment of the gene expression program. The hypoxia inducible factor-1 (HIF-1) is a transcription factor that mediates the adaptive responses to the reduction in oxygen availability. HIF-1 activation in hypoxic conditions promotes the survival of cells through the induction of adaptive genes involved in glucose and energy production, glucose transport, cell proliferation, cell survival, iron homeostasis, erythropoiesis, angiogenesis and vascular reactivity. In recent years, biomedical research has focused on the oxygen regulated α subunit of HIF-1 as a potential therapy in medical events that involve hypoxic conditions. In this review we summarize current knowledge on the use of HIF-1α as a therapeutic target against cerebral ischemia through two different strategies: 1) the use of ischemic preconditioning to induce the HIF-1 pathway regulation, and 2) the pharmacological inhibition of prolyl and asparaginyl hydroxylases. Both strategies appear as attractive options for protection in ischemia in which signaling pathway activation could contribute to the establishment of tolerance in brain.
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Aguilera Penelope, Vazquez-Contreras Edgar, Gomez-Martínez Daniel Carlos and Cardenas Elena Chanez Maria, Hypoxia Inducible Factor-1 as a Therapeutic Target in Cerebral Ischemia, Current Signal Transduction Therapy 2009; 4 (3) . https://dx.doi.org/10.2174/157436209789057458
DOI https://dx.doi.org/10.2174/157436209789057458 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
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