ArticleJournal of molecular and cellular cardiology2008
Cyclin-dependent kinase 2 signaling regulates myocardial ischemia/reperfusion injury.
Article in Journal of molecular and cellular cardiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- The role of HDAC3 and its inhibitors in regulation of oxidative stress and chronic diseases.Cell death discovery · 2023Review
- Discovery of cancer-preventive juices reactivating RB functions.Environmental health and preventive medicine · 2023Article
- Loss of Rbl2 (Retinoblastoma-Like 2) Exacerbates Myocardial Ischemia/Reperfusion Injury.Journal of the American Heart Association · 2022Article
- The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury.Cell death & disease · 2021Review
- Network-based computational approach to identify genetic links between cardiomyopathy and its risk factors.IET systems biology · 2020Article
- Cell Cycle Proteins as Key Regulators of Postmitotic Cell Death.The Yale journal of biology and medicine · 2019Review
- Degradation of GRK2 and AKT is an early and detrimental event in myocardial ischemia/reperfusion.EBioMedicine · 2019Article
- Inhibition of cyclin-dependent kinase 2 protects against doxorubicin-induced cardiomyocyte apoptosis and cardiomyopathy.The Journal of biological chemistry · 2018Article
- Differential requirement of cyclin-dependent kinase 2 for oligodendrocyte progenitor cell proliferation and differentiation.Cell division · 2012Article
- The role of E2F-1 and downstream target genes in mediating ischemia/reperfusion injury in vivo.Journal of molecular and cellular cardiology · 2011Article
- Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes.Nature reviews. Drug discovery · 2011Review
- Protection of cisplatin cytotoxicity by an inactive cyclin-dependent kinase.American journal of physiology. Renal physiology · 2010Article
- Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice.The Journal of clinical investigation · 2010Article
- Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin D1 expression in vivo.Cell cycle (Georgetown, Tex.) · 2009Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Ischemia/reperfusion (I/R) injury to the heart is accompanied by the upregulation and posttranslational modification of a number of proteins normally involved in regulating cell cycle progression. Two such proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene product (Rb), also play a critical role in the control of apoptosis. Myocardial ischemia activates Cdk2, resulting in the phosphorylation and inactivation of Rb. Blocking Cdk2 activity reduces apoptosis in cultured cardiac myocytes. Genetic or pharmacological inhibition of Cdk2 activity in vivo during I/R injury led to a 36% reduction in infarct size (IFS), when compared to control mice, associated with a reduction in apoptotic myocytes. To confirm that Rb was the critical target in Cdk2-mediated I/R injury, we determined the consequences of I/R injury in cardiac-specific Rb-deficient mice (CRb(L/L)). IFS was increased 140% in CRb(L/L) mice compared to CRb+/+ controls. TUNEL positive nuclei and caspase-3 activity were augmented by 92% and 36%, respectively, following injury in the CRb(L/L) mice demonstrating that loss of Rb in the heart significantly exacerbates I/R injury. These data suggest that Cdk2 signaling pathways are critical regulators of cardiac I/R injury in vivo and support a cardioprotective role for Rb.
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Registered trials
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.