ArticleCirculation research2010
Activation of PKN mediates survival of cardiac myocytes in the heart during ischemia/reperfusion.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Dissecting the Phospho-Regulatory Landscape of Protein Kinase N1 (PKN1) and Its Downstream Signaling: Functional Insights into the Activity-Dependent and Disease-Relevant Phosphosites.International journal of molecular sciences · 2026Article
- Phosphorylation of CRYAB induces a condensatopathy to worsen post-myocardial infarction left ventricular remodeling.The Journal of clinical investigation · 2025Article
- Lipid-Binding Regions within PKC-Related Serine/Threonine Protein Kinase N1 (PKN1) Required for Its Regulation.Biochemistry · 2024Article
- Myocardial Protection and Current Cancer Therapy: Two Opposite Targets with Inevitable Cost.International journal of molecular sciences · 2022Review
- PKN2 deficiency leads both to prenatal 'congenital' cardiomyopathy and defective angiotensin II stress responses.The Biochemical journal · 2022Article
- Alpha B-Crystallin in Muscle Disease Prevention: The Role of Physical Activity.Molecules (Basel, Switzerland) · 2022Review
- Review
- The structure and function of protein kinase C-related kinases (PRKs).Biochemical Society transactions · 2021Review
- PKN1 Is a Novel Regulator of Hippocampal GluA1 Levels.Frontiers in synaptic neuroscience · 2021Article
- Role of DJ-1 in Modulating Glycative Stress in Heart Failure.Journal of the American Heart Association · 2020Article
- PKN1 kinase-negative knock-in mice develop splenomegaly and leukopenia at advanced age without obvious autoimmune-like phenotypes.Scientific reports · 2019Article
- Characterization of the novel cardiolipin binding regions identified on the protease and lipid activated PKC-related kinase 1.Protein science : a publication of the Protein Society · 2019Article
- l-α-Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK-dependent pathway.Pharmacology research & perspectives · 2019Article
- PKC and PKN in heart disease.Journal of molecular and cellular cardiology · 2019Review
- Loss of Protein Kinase Novel 1 (PKN1) is associated with mild systolic and diastolic contractile dysfunction, increased phospholamban Thr17 phosphorylation, and exacerbated ischaemia-reperfusion injury.Cardiovascular research · 2018Article
- Article
- Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation.Scientific reports · 2016Article
- The effects of phosphodiesterase-5 inhibitor sildenafil against post-resuscitation myocardial and intestinal microcirculatory dysfunction by attenuating apoptosis and regulating microRNAs expression: essential role of nitric oxide syntheses signaling.Journal of translational medicine · 2015Article
- Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies.Antioxidants & redox signaling · 2014Review
- Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons.Current neuropharmacology · 2014Article
Corrections and comments
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Authors and funding
11 authors at 1 institution.
Funding
Abstract
rationaleThe function of PKN, a stress-activated protein kinase, in the heart is poorly understood.
objectiveWe investigated the functional role of PKN during myocardial ischemia/reperfusion (I/R). METHODS AND
resultsPKN is phosphorylated at Thr774 in hearts subjected to ischemia and reperfusion. Myocardial infarction/area at risk (MI/AAR) produced by 45 minutes of ischemia and 24 hours of reperfusion was significantly smaller in transgenic mice with cardiac-specific overexpression of constitutively active (CA) PKN (Tg-CAPKN) than in nontransgenic (NTg) mice (15+/-5 versus 38+/-5%, P<0.01). The number of TUNEL-positive nuclei was significantly lower in Tg-CAPKN (0.3+/-0.2 versus 1.0+/-0.2%, P<0.05). Both MI/AAR (63+/-9 versus 45+/-8%, P<0.05) and the number of TUNEL-positive cells (7.9+/-1.0 versus 1.3+/-0.9%, P<0.05) were greater in transgenic mice with cardiac-specific overexpression of dominant negative PKN (Tg-DNPKN) than in NTg mice. Thr774 phosphorylation of PKN was also observed in response to H(2)O(2) in cultured cardiac myocytes. Stimulation of PKN prevented, whereas inhibition of PKN aggravated, cell death induced by H(2)O(2), suggesting that the cell-protective effect of PKN is cell-autonomous in cardiac myocytes. PKN induced phosphorylation of alpha B crystallin and increased cardiac proteasome activity. The infarct reducing effect in Tg-CAPKN mice was partially inhibited by epoxomicin, a proteasome inhibitor.
conclusionsPKN is activated by I/R and inhibits apoptosis of cardiac myocytes, thereby protecting the heart from I/R injury. PKN mediates phosphorylation of alpha B crystallin and stimulation of proteasome activity, which, in part, mediates the protective effect of PKN in the heart.
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Registered trials
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