Mitochondrial protein kinase Cϵ (PKCϵ): emerging role in cardiac protection from ischaemic damage

2007 ◽  
Vol 35 (5) ◽  
pp. 1052-1054 ◽  
Author(s):  
G.R. Budas ◽  
D. Mochly-Rosen
Keyword(s):  
Protein Kinase ◽  
Reperfusion Injury ◽  
Mitochondrial Permeability Transition ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Permeability Transition ◽  
K Channel ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

Mitochondria mediate diverse cellular functions including energy generation and ROS (reactive oxygen species) production and contribute to signal transduction. Mitochondria are also key regulators of cell viability and play a central role in necrotic and apoptotic cell death pathways induced by cardiac ischaemia/reperfusion injury. PKC (protein kinase C) ϵ plays a critical role in cardioprotective signalling pathways that protect the heart from ischaemia/reperfusion. Emerging evidence suggests that the cardioprotective target of PKCϵ resides at the mitochondria. Proposed mitochondrial targets of PKCϵ include mitoKATP (mitochondrial ATP-sensitive K+ channel), components of the MPTP (mitochondrial permeability transition pore) and components of the electron transport chain. This review highlights mitochondrial targets of PKCϵ and their possible role in cardioprotective signalling in the setting of ischaemia/reperfusion injury.

scholarly journals Effects of Cardiovascular Risk Factors on Cardiac STAT3

2018 ◽  
Vol 19 (11) ◽  
pp. 3572 ◽  
Author(s):  
Márton Pipicz ◽  
Virág Demján ◽  
Márta Sárközy ◽  
Tamás Csont
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Reperfusion Injury ◽  
Cardiovascular Risk Factors ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Cardiac Cells ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Age Related

Nuclear, mitochondrial and cytoplasmic signal transducer and activator of transcription 3 (STAT3) regulates many cellular processes, e.g., the transcription or opening of mitochondrial permeability transition pore, and its activity depends on the phosphorylation of Tyr705 and/or Ser727 sites. In the heterogeneous network of cardiac cells, STAT3 promotes cardiac muscle differentiation, vascular element formation and extracellular matrix homeostasis. Overwhelming evidence suggests that STAT3 is beneficial for the heart, plays a role in the prevention of age-related and postpartum heart failure, protects the heart against cardiotoxic doxorubicin or ischaemia/reperfusion injury, and is involved in many cardioprotective strategies (e.g., ischaemic preconditioning, perconditioning, postconditioning, remote or pharmacological conditioning). Ischaemic heart disease is still the leading cause of death worldwide, and many cardiovascular risk factors contribute to the development of the disease. This review focuses on the effects of various cardiovascular risk factors (diabetes, aging, obesity, smoking, alcohol, depression, gender, comedications) on cardiac STAT3 under non-ischaemic baseline conditions, and in settings of ischaemia/reperfusion injury with or without cardioprotective strategies.

Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology

2015 ◽  
Vol 113 (03) ◽  
pp. 513-521 ◽  
Author(s):  
Sang-Bing Ong ◽  
Andrew Hall ◽  
Rachel Dongworth ◽  
Siavash Kalkhoran ◽  
Aswin Pyakurel ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mitochondrial Permeability Transition ◽  
Cardiac Cells ◽  
Mitochondrial Morphology ◽  
Myocardial Infarct Size ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Mptp Opening ◽  
Ischaemia Reperfusion ◽  
Mitochondrial Elongation

SummaryThe mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.0 % caAkt vs 49 ± 5.8 % control: N=80 cells/group; p< 0.05). This effect was associated with delayed time taken to induce mitochondrial permeability transition pore (MPTP) opening (by 2.4 ± 0.5 fold; N=80 cells/group: p< 0.05); and reduced cell death following simulated IRI (32.8 ± 1.2 % caAkt vs 63.8 ± 5.6 % control: N=320 cells/group: p< 0.05). Similar effects on mitochondrial morphology, MPTP opening, and cell survival post-IRI, were demonstrated with pharmacological activation of Akt using the known cardioprotective cytokine, erythropoietin (EPO). The effect of Akt on inducing mitochondrial elongation was found to be dependent on the mitochondrial fusion protein, Mitofusin-1 (Mfn1), as ablation of Mfn1 in mouse embryonic fibroblasts (MEFs) abrogated Akt-mediated mitochondrial elongation. Finally, in vivo pre-treatment with EPO reduced myocardial infarct size (as a % of the area at risk) in adult mice subjected to IRI (26.2 ± 2.6 % with EPO vs 46.1 ± 6.5 % in control; N=7/group: p< 0.05), and reduced the proportion of cells displaying myofibrillar disarray and mitochondrial fragmentation observed by electron microscopy in adult murine hearts subjected to ischaemia from 5.8 ± 1.0 % to 2.2 ± 1.0 % (N=5 hearts/group; p< 0.05). In conclusion, we found that either genetic or pharmacological activation of Akt protected the heart against acute ischaemia-reperfusion injury by modulating mitochondrial morphology.

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