Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1

Cai, Zhejun; Bosch–Marcé, Marta; Fox-Talbot, Karen; Wang, Lei; Wei, Chiming; Trush, Michael A.; Semenza, Gregg L.

doi:10.1093/cvr/cvm035

Cited by 220 publications

(188 citation statements)

References 55 publications

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“…Although HIF-1α +/− heterozygous mice develop normally, partial HIF-1α deficiency results in significantly impaired responses to hypoxia and ischemia (1,7,15,26). The administration of 200 ppm of acrylamide in drinking water for 1 wk did not cause distal limb weakness in WT HIF-1α +/+ mice, whereas this dose was sufficient to cause significant distal limb weakness in HIF-1α +/− littermate mice (Fig.…”

Section: No Donor Administration Prevents Axonal Degeneration Ex Vivomentioning

confidence: 92%

“…In both brain (5, 6) and heart (7,8), HIF-1 activation is critical to ischemic preconditioning, which represents the endogenous biological phenomenon in which a sublethal hypoxic-ischemic insult induces protection against future lethal insults. HIF-1 is the transcriptional activator of several genes that potentially may be involved in the neuroprotection associated with ischemic preconditioning, including erythropoietin (EPO), vascular endothelial growth factor, glycolytic enzymes, heme oxygenase, glucose transporters, and neuroglobin (9).…”

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confidence: 99%

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Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Keswani

Bosch–Marcé

Reed

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Nitric oxide (NO) is a signaling molecule that can trigger adaptive (physiological) or maladaptive (pathological) responses to stress stimuli in a context-dependent manner. We have previously reported that NO may signal axonal injury to neighboring glial cells. In this study, we show that mice deficient in neuronal nitric oxide synthase (nNOS −/− ) are more vulnerable than WT mice to toxin-induced peripheral neuropathy. The administration of NO donors to primary dorsal root ganglion cultures prevents axonal degeneration induced by acrylamide in a dose-dependent manner. We demonstrate that NO-induced axonal protection is dependent on hypoxia-inducible factor (HIF)-1-mediated transcription of erythropoietin (EPO) within glial (Schwann) cells present in the cultures. Transduction of Schwann cells with adenovirus AdCA5 encoding a constitutively active form of HIF-1α results in amelioration of acrylamide-induced axonal degeneration in an EPOdependent manner. Mice that are partially deficient in HIF-1α (HIF-1α +/− ) are also more susceptible than WT littermates to toxic neuropathy. Our results indicate that NO→HIF-1→EPO signaling represents an adaptive mechanism that protects against axonal degeneration.

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Section: No Donor Administration Prevents Axonal Degeneration Ex Vivomentioning

confidence: 92%

mentioning

confidence: 99%

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Keswani

Bosch–Marcé

Reed

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, it seems that Hif-2␣-dependent genes could have major roles in cardiac preconditioning, at least in the form triggered by sustained (or long-lasting) hypoxia. This observation is appealing because although Hif-1␣ is known to participate in hypoxic/ischemic cardioprotection, 8,25,34 the involvement in this process of exclusive Hif-2␣-dependent genes was not suspected. However, Hif-2␣ has been suggested to contribute to the protective adaptive responses of kidney tissue 10 and neurons 11 to ischemia, and there are data indicating that Hif-2␣ is necessary for the regulation of antioxidant genes.…”

Section: Bautista Et Almentioning

confidence: 99%

“…9,25 Therefore, it seems that Hif-2␣ has several as yet unknown unique aspects pertinent to ischemia/reperfusion biology in the heart and possibly other organs. It must be stressed that most previous studies have used alternating short-lasting (few minutes) exposures to ischemia/reperfusion 8 and that in our experiments, we exposed the cells to sustained hypoxia (8 to 24 hours). The mechanisms involved in these 2 forms of cardioprotection might be different and not mutually exclusive.…”

Section: Bautista Et Almentioning

confidence: 99%

“…5 There are numerous well-studied Hif-1␣-regulated genes, 6,7 and some of them participate in cardiac ischemic preconditioning. 8 Whether there are genes selectively regulated by Hif-2␣ is under debate, and the role of Hif-2␣ in adaptation of cardiomyocytes to hypoxia is unknown. 9 Hif-2␣ has, however, been suggested to participate in the protective adaptive responses of kidney tissue 10 and neurons 11 to ischemia.…”

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confidence: 99%

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Hypoxia Inducible Factor-2α Stabilization and Maxi-K ⁺ Channel β ₁ -Subunit Gene Repression by Hypoxia in Cardiac Myocytes

Bautista

Castro

López‐Barneo

et al. 2009

Circulation Research

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Abstract-The Ca 2ϩ -and voltage-dependent K ϩ (maxi-K) channel ␤ 1 -subunit mRNA is particularly abundant in cardiomyocytes but its functional role is unknown. This is intriguing because functional maxi-K channels are not found in cardiomyocyte plasmalemma, although they have been suggested to be in the inner mitochondrial membrane and participate in cardioprotection. We report here that ␤ 1 protein may interact with mitochondrial proteins and that the ␤ 1 -subunit gene (KCNMB1) is repressed by sustained hypoxia in dispersed cardiomyocytes as well as in heart intact tissue. The effect of hypoxia is time-and dose-dependent, is mimicked by addition of reactive oxygen species, and selectively requires hypoxia inducible factor-2␣ (Hif-2␣) stabilization. We have observed that adaptation to hypoxia exerts a protective role on cardiomyocytes subjected to ischemia and that, unexpectedly, this form of preconditioning absolutely depends on Hif-2␣. Interference of the ␤ 1 -subunit mRNA increases cardiomyocyte resistance to ischemia. Therefore, Hif-2␣-mediated ␤ 1 -subunit gene repression is a previously unknown mechanism that could participate in the gene expression program triggered by sustained hypoxia to prevent deleterious mitochondrial depolarization and ATP deficiency in cardiac cells. Key Words: hypoxia inducible factor-2␣ Ⅲ hypoxic preconditioning Ⅲ maxi-K channel ␤ 1 -subunit Ⅲ cardiomyocyte Ⅲ small interfering RNA

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Cellular and molecular mechanisms in the hypoxic tissue: role of HIF‐1 and ROS

Zepeda

Pessoa

Castillo

et al. 2013

Cell Biochemistry & Function

115

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Reactive oxygen species such as superoxide anion radicals (O2 (-) ) and hydrogen peroxide (H2 O2 ) have for long time been recognized as undesirable by-products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiological conditions such as those activated in hypoxic microenvironments. The molecular response to hypoxia requires fast-acting mechanisms acting within a wide range of partial pressures of oxygen (O2 ). Intracellular O2 sensing is an evolutionary preserved feature, and the best characterized molecular responses to hypoxia are mediated through transcriptional activation. The transcription factor, hypoxia-inducible factor 1 (HIF-1), is a critical mediator of these adaptive responses, and its activation by hypoxia involves O2 -dependent posttranslational modifications and nuclear translocation. Through the induction of the expression of its target genes, HIF-1 coordinately regulates tissue O2 supply and energetic metabolism. Other transcription factors such as nuclear factor κB are also redox sensitive and are activated in pro-oxidant and hypoxic conditions. The purpose of this review is to summarize new developments in HIF-mediated O2 sensing mechanisms and their interactions with reactive oxygen species-generating pathways in normal and abnormal physiology.

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Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1

Abstract: HIF-1 alpha is required for IPC-induced mitochondrial ROS production and myocardial protection against ischaemia-reperfusion injury.

Cited by 220 publications

References 55 publications

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Hypoxia Inducible Factor-2α Stabilization and Maxi-K ⁺ Channel β ₁ -Subunit Gene Repression by Hypoxia in Cardiac Myocytes

Cellular and molecular mechanisms in the hypoxic tissue: role of HIF‐1 and ROS

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Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1

Abstract: HIF-1 alpha is required for IPC-induced mitochondrial ROS production and myocardial protection against ischaemia-reperfusion injury.

Cited by 220 publications

References 55 publications

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Hypoxia Inducible Factor-2α Stabilization and Maxi-K + Channel β 1 -Subunit Gene Repression by Hypoxia in Cardiac Myocytes

Cellular and molecular mechanisms in the hypoxic tissue: role of HIF‐1 and ROS

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Hypoxia Inducible Factor-2α Stabilization and Maxi-K ⁺ Channel β ₁ -Subunit Gene Repression by Hypoxia in Cardiac Myocytes