ArticleCirculation research2023
Interdependent Nuclear Co-Trafficking of ASPP1 and p53 Aggravates Cardiac Ischemia/Reperfusion Injury.
Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
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- Hspa1b attenuates hypoxia/reoxygenation-induced cardiomyocyte injury through dual suppression of P53-driven apoptotic and ferroptotic pathways.Cell stress & chaperones · 2026Article
- [Targeted inhibition of miR-503 upregulates Apelin expression to alleviate myocardial infarction in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- A Comprehensive Bibliometric and Visual Analysis of EGR1 in Cardiovascular Disease.Molecular biotechnology · 2026Review
- Systematic Pharmacology Combined With Experimental Validation Reveals the Apoptosis-Related Mechanism of Simiao Yong'an (SMYA) Decoction Against Myocardial Ischemia-Reperfusion Injury.Cardiovascular therapeutics · 2026Article
- BAK and BAX: Therapeutic Targets for Acute Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury.Biology · 2025Review
- Acute Myocardial Infarction: Molecular Pathogenesis, Diagnosis, and Clinical Management.MedComm · 2025Review
- The PIWI-interacting RNA CRAPIR alleviates myocardial ischemia‒reperfusion injury by reducing p53-mediated apoptosis via binding to SRSF1.Acta pharmacologica Sinica · 2025Article
- Mechanisms of programmed cell death in livestock follicular development and atresia: a review.Journal of animal science and biotechnology · 2025Review
- Inhibitors of p53 Apoptosis-Stimulating Protein Mitigate Acute Kidney Injury by Modulating the HIF-1α/SLC7A11 Pathway to Suppress Ferroptosis.Journal of cellular and molecular medicine · 2025Article
- cIAP2-mediated IGF2BP2 ubiquitination and degradation regulate cardiomyocyte apoptosis via stabilizing mCell biology and toxicology · 2025Article
- eIF4A1 exacerbates myocardial ischemia-reperfusion injury in mice by promoting nuclear translocation of transgelin/p53.Acta pharmacologica Sinica · 2025Article
- Semaglutide administration protects cardiomyocytes in db/db mice via energetic improvement and mitochondrial quality control.Acta pharmacologica Sinica · 2025Article
- Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics.Scientific reports · 2025Article
- AKR1C3 protects cardiomyocytes against hypoxia-induced cell apoptosis through the Nrf-2/NF-κB pathway.Acta biochimica et biophysica Sinica · 2025Article
- Mettl1 knockdown alleviates cardiac I/R injury in mice by inactivating the Mettl1-CYLD-P53 positive feedback loop.Acta pharmacologica Sinica · 2025Article
- Review
- Identification of novel target genes in exaggerated cardiac remodeling following myocardial infarction in diabetes.Frontiers in endocrinology · 2025Article
Corrections and comments
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Authors and funding
25 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveASPP1 (apoptosis stimulating of p53 protein 1) is critical in regulating cell apoptosis as a cofactor of p53 to promote its transcriptional activity in the nucleus. However, whether cytoplasmic ASPP1 affects p53 nuclear trafficking and its role in cardiac diseases remains unknown. This study aims to explore the mechanism by which ASPP1 modulates p53 nuclear trafficking and the subsequent contribution to cardiac ischemia/reperfusion (I/R) injury. METHODS AND
resultsThe immunofluorescent staining showed that under normal condition ASPP1 and p53 colocalized in the cytoplasm of neonatal mouse ventricular cardiomyocytes, while they were both upregulated and translocated to the nuclei upon hypoxia/reoxygenation treatment. The nuclear translocation of ASPP1 and p53 was interdependent, as knockdown of either ASPP1 or p53 attenuated nuclear translocation of the other one. Inhibition of importin-β1 resulted in the cytoplasmic sequestration of both p53 and ASPP1 in neonatal mouse ventricular cardiomyocytes with hypoxia/reoxygenation stimulation. Overexpression of ASPP1 potentiated, whereas knockdown of ASPP1 inhibited the expression of Bax (Bcl2-associated X), PUMA (p53 upregulated modulator of apoptosis), and Noxa, direct apoptosis-associated targets of p53. ASPP1 was also increased in the I/R myocardium. Cardiomyocyte-specific transgenic overexpression of ASPP1 aggravated I/R injury as indicated by increased infarct size and impaired cardiac function. Conversely, knockout of ASPP1 mitigated cardiac I/R injury. The same qualitative data were observed in neonatal mouse ventricular cardiomyocytes exposed to hypoxia/reoxygenation injury. Furthermore, inhibition of p53 significantly blunted the proapoptotic activity and detrimental effects of ASPP1 both in vitro and in vivo.
conclusionsBinding of ASPP1 to p53 triggers their nuclear cotranslocation via importin-β1 that eventually exacerbates cardiac I/R injury. The findings imply that interfering the expression of ASPP1 or the interaction between ASPP1 and p53 to block their nuclear trafficking represents an important therapeutic strategy for cardiac I/R injury.
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