Dataset Information

Hypoxic preconditioning protection is eliminated in HIF-1? knockout mice subjected to neonatal hypoxia-ischemia.

ABSTRACT: Hypoxic preconditioning (HPc) protects the neonatal brain in the setting of hypoxia-ischemia (HI). The mechanisms of protection may depend on activation of hypoxia-inducible factor (HIF-1?). This study sought to clarify the role of HIF-1? after HPc and HI.To induce HPc, HIF-1? knockout and wild-type (WT) mice were exposed to hypoxia at postnatal day 6. At day 7, the mice underwent HI. Brain injury was determined by histology. HIF-1?, downstream targets, and markers of cell death were measured by western blot.HPc protected the WT brain compared with WT without HPc, but did not protect the HIF-1? knockout brain. In WT, HIF-1? increased after hypoxia and after HI, but not with HPc. The HIF-1? knockout showed no change in HIF-1? after hypoxia, HI, or HPc/HI. After HI, spectrin 145/150 was higher in HIF-1? knockout, but after HPc/HI, it was higher in WT. Lysosome-associated membrane protein was higher in WT early after HI, but not later. After HPc/HI, lysosome-associated membrane protein was higher in HIF-1? knockout.These results indicate that HIF-1? is necessary for HPc protection in the neonatal brain and may affect cell death after HI. Different death and repair mechanisms depend on the timing of HPc.

SUBMITTER: Sheldon RA

PROVIDER: S-EPMC4167022 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypoxic preconditioning protection is eliminated in HIF-1α knockout mice subjected to neonatal hypoxia-ischemia.

Sheldon R Ann RA Lee Christina L CL Jiang Xiangning X Knox Renatta N RN Ferriero Donna M DM

Pediatric research 20140408 1

<h4>Background</h4>Hypoxic preconditioning (HPc) protects the neonatal brain in the setting of hypoxia-ischemia (HI). The mechanisms of protection may depend on activation of hypoxia-inducible factor (HIF-1α). This study sought to clarify the role of HIF-1α after HPc and HI.<h4>Methods</h4>To induce HPc, HIF-1α knockout and wild-type (WT) mice were exposed to hypoxia at postnatal day 6. At day 7, the mice underwent HI. Brain injury was determined by histology. HIF-1α, downstream targets, and mar ...[more]

PMID: 24713818

Similar Datasets

Project description:BackgroundHypoxia-inducible factor (HIF)-1 is involved in the regulation of hypoxic preconditioning in cardiomyocytes. Under hypoxic conditions, HIF-1α accumulates and is translocated to the nucleus, where it forms an active complex with HIF-1β and activates transcription of approximately 60 kinds of hypoxia-adaptive genes. Microtubules are hollow tubular structures in the cell that maintain cellular morphology and that transport substances. This study attempted to clarify the role of microtubule structure in the endonuclear aggregation of HIF-1α following hypoxic preconditioning of cardiomyocytes.MethodsPrimary rat cardiomyocytes were isolated and cultured. The cardiomyocyte culture system was used to establish a hypoxia model and a hypoxic preconditioning model. Interventions were performed on primary cardiomyocytes using a microtubule-depolymerizing agent and different concentrations of a microtubule stabilizer. The microtubule structure and the degree of HIF-1α nuclear aggregation were observed by confocal laser scanning microscopy. The expression of HIF-1α in the cytoplasm and nucleus was detected using Western blotting. Cardiomyocyte energy content, reflected by adenosine triphosphate/adenosine diphosphate (ATP/ADP), and key glycolytic enzymes were monitored by colorimetry and high-performance liquid chromatography (HPLC). Reactive oxygen species (ROS) production was also used to comprehensively assess whether microtubule stabilization can enhance the myocardial protective effect of hypoxic preconditioning.ResultsDuring prolonged hypoxia, it was found that the destruction of the microtubule network structure of cardiomyocytes was gradually aggravated. After this preconditioning, an abundance of HIF-1α was clustered in the nucleus. When the microtubules were depolymerized and hypoxia pretreatment was performed, HIF-1α clustering occurred around the nucleus, and HIF-1α nuclear expression was low. The levels of key glycolytic enzymes were significantly higher in the microtubule stabilizer group than in the hypoxia group. Additionally, the levels of lactate dehydrogenase and ROS were significantly lower in the microtubule stabilizer group than in the hypoxia group.ConclusionThe microtubules of cardiomyocytes may be involved in the process of HIF-1α endonuclear aggregation, helping to enhance the anti-hypoxic ability of cardiomyocytes.

Dataset Information

Hypoxic preconditioning protection is eliminated in HIF-1? knockout mice subjected to neonatal hypoxia-ischemia.

Publications

Hypoxic preconditioning protection is eliminated in HIF-1α knockout mice subjected to neonatal hypoxia-ischemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets