ArticleCell death & disease2021
The hypoxia sensitive metal transcription factor MTF-1 activates NCX1 brain promoter and participates in remote postconditioning neuroprotection in stroke.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Impact of remote ischemic postconditioning on acute ischemic stroke in China: a systematic review and meta-analysis of randomized controlled trials.Systematic reviews · 2024Pooled it
- Early Transcriptional Changes in Neutrophil-Mediated Processes Following Recanalization After Ischemic Stroke.Journal of the American Heart Association · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Chronic hindlimb ischemia exacerbates ischemic stroke by disrupting cerebral hemodynamics and glycerophospholipid metabolism in mice.Scientific reports · 2026Article
- Zinc-Induced PKCδ-dependent Phosphorylation of MTF-1 Promotes Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension.International journal of biological sciences · 2026Article
- TP53I11 Functions Downstream of Multiple MicroRNAs to Increase ER Calcium Levels and Inhibits Cancer Cell Proliferation.International journal of molecular sciences · 2024Article
- Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development.Metallomics : integrated biometal science · 2024Review
- Article
- Longitudinal Neuropathological Consequences of Extracranial Radiation Therapy in Mice.International journal of molecular sciences · 2024Article
- Remote limb ischemic postconditioning inhibits microglia pyroptosis by modulating HGF after acute ischemia stroke.Bioengineering & translational medicine · 2023Article
- Effects of Zinc on the Right Cardiovascular Circuit in Long-Term Hypobaric Hypoxia in Wistar Rats.International journal of molecular sciences · 2023Article
- Comprehensive analysis of cuproptosis-related genes in immune infiltration in ischemic stroke.Frontiers in neurology · 2022Article
- Remote Limb Ischemic Postconditioning Protects Against Ischemic Stroke by Promoting Regulatory T Cells Thriving.Journal of the American Heart Association · 2021Article
- Emerging Role of microRNAs in Stroke Protection Elicited by Remote Postconditioning.Frontiers in neurology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Remote limb ischemic postconditioning (RLIP) is an experimental strategy in which short femoral artery ischemia reduces brain damage induced by a previous harmful ischemic insult. Ionic homeostasis maintenance in the CNS seems to play a relevant role in mediating RLIP neuroprotection and among the effectors, the sodium-calcium exchanger 1 (NCX1) may give an important contribution, being expressed in all CNS cells involved in brain ischemic pathophysiology. The aim of this work was to investigate whether the metal responsive transcription factor 1 (MTF-1), an important hypoxia sensitive transcription factor, may (i) interact and regulate NCX1, and (ii) play a role in the neuroprotective effect mediated by RLIP through NCX1 activation. Here we demonstrated that in brain ischemia induced by transient middle cerebral occlusion (tMCAO), MTF-1 is triggered by a subsequent temporary femoral artery occlusion (FAO) and represents a mediator of endogenous neuroprotection. More importantly, we showed that MTF-1 translocates to the nucleus where it binds the metal responsive element (MRE) located at -23/-17 bp of Ncx1 brain promoter thus activating its transcription and inducing an upregulation of NCX1 that has been demonstrated to be neuroprotective. Furthermore, RLIP restored MTF-1 and NCX1 protein levels in the ischemic rat brain cortex and the silencing of MTF-1 prevented the increase of NCX1 observed in RLIP protected rats, thus demonstrating a direct regulation of NCX1 by MTF-1 in the ischemic cortex of rat exposed to tMCAO followed by FAO. Moreover, silencing of MTF-1 significantly reduced the neuroprotective effect elicited by RLIP as demonstrated by the enlargement of brain infarct volume observed in rats subjected to RLIP and treated with MTF-1 silencing. Overall, MTF-dependent activation of NCX1 and their upregulation elicited by RLIP, besides unraveling a new molecular pathway of neuroprotection during brain ischemia, might represent an additional mechanism to intervene in stroke pathophysiology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.