ArticleCardiovascular research2015
PKCε-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 100 citations in OpenAlex.
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- Dietary Leucine Requirement and Its Effects on Growth, Immunity, Antioxidant Capacity and Protein Metabolism in Pacific White Shrimp, Penaeus vannamei.Marine biotechnology (New York, N.Y.) · 2026Article
- Targeting the bile acid receptor TGR5 with Gentiopicroside to activate Nrf2 antioxidant signaling and mitigate Parkinson's disease in an MPTP mouse model.Journal of advanced research · 2026Article
- Fisetin alleviates oxidative stress and promotes porcine early embryonic development via activation of the NRF2-ARE signalling pathway.Animal bioscience · 2025Article
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Endothelial Dysfunction in the Tubule Area Accelerates the Progression of Early Diabetic Kidney Disease.Physiological research · 2024Article
- Protein Kinase C (PKC) in Neurological Health: Implications for Alzheimer's Disease and Chronic Alcohol Consumption.Brain sciences · 2024Review
- Harnessing peroxisome proliferator-activated receptor γ agonists to induce Heme Oxygenase-1: a promising approach for pulmonary inflammatory disorders.Cell communication and signaling : CCS · 2024Review
- Interplay between Protein Kinase C Epsilon and Reactive Oxygen Species during Myogenic Differentiation.Cells · 2023Article
- Protectin conjugates in tissue regeneration 1 alleviates sepsis-induced acute lung injury by inhibiting ferroptosis.Journal of translational medicine · 2023Article
- Effects of antioxidants on diabetic kidney diseases: mechanistic interpretations and clinical assessment.Chinese medicine · 2023Review
- Nrf2-Mediated Dichotomy in the Vascular System: Mechanistic and Therapeutic Perspective.Cells · 2022Review
- Mechanism of CREB1 in cardiac function of rats with heart failure via regulating the microRNA-376a-3p/TRAF6 axis.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Article
- Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy.Nutrition & diabetes · 2022Article
- Menthae Herba Attenuates Neuroinflammation by Regulating CREB/Nrf2/HO-1 Pathway in BV2 Microglial Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Polydatin protects neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling.Molecular medicine reports · 2022Article
- Human umbilical cord mesenchymal stem cells reduce oxidative damage and apoptosis in diabetic nephropathy by activating Nrf2.Stem cell research & therapy · 2021Article
- Nrf2 induces Ucp1 expression in adipocytes in response to β3-AR stimulation and enhances oxygen consumption in high-fat diet-fed obese mice.BMB reports · 2021Article
- Dexmedetomidine ameliorates endotoxin-induced acute lung injury in vivo and in vitro by preserving mitochondrial dynamic equilibrium through the HIF-1a/HO-1 signaling pathway.Redox biology · 2021Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsVascular injury leading to endothelial dysfunction is a characteristic feature of chronic renal disease, diabetes mellitus, and systemic inflammatory conditions, and predisposes to apoptosis and atherogenesis. Thus, endothelial dysfunction represents a potential therapeutic target for atherosclerosis prevention. The observation that activity of either protein kinase C epsilon (PKCε) or haem oxygenase-1 (HO-1) enhances endothelial cell (EC) resistance to inflammation and apoptosis led us to test the hypothesis that HO-1 is a downstream target of PKCε. METHODS AND
resultsExpression of constitutively active PKCε in human EC significantly increased HO-1 mRNA and protein, whereas conversely aortas or cardiac EC from PKCε-deficient mice exhibited reduced HO-1 when compared with wild-type littermates. Angiotensin II activated PKCε and induced HO-1 via a PKCε-dependent pathway. PKCε activation significantly attenuated TNFα-induced intercellular adhesion molecule-1, and increased resistance to serum starvation-induced apoptosis. These responses were reversed by the HO antagonist zinc protoporphyrin IX. Phosphokinase antibody array analysis identified CREB1((Ser133)) phosphorylation as a PKCε signalling intermediary, and cAMP response element-binding protein 1 (CREB1) siRNA abrogated PKCε-induced HO-1 up-regulation. Likewise, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was identified as a PKCε target using nuclear translocation and DNA-binding assays, and Nrf2 siRNA prevented PKCε-mediated HO-1 induction. Moreover, depletion of CREB1 inhibited PKCε-induced Nrf2 DNA binding, suggestive of transcriptional co-operation between CREB1 and Nrf2.
conclusionsPKCε activity in the vascular endothelium regulates HO-1 via a pathway requiring CREB1 and Nrf2. Given the potent protective actions of HO-1, we propose that this mechanism is an important contributor to the emerging role of PKCε in the maintenance of endothelial homeostasis and resistance to injury.
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