Abstract
Alterations in protein kinase C (PKC) isozymes and mitochondrial functions such as oxidative phosphorylation (OXPHOS) and apoptosis have each been implicated in human diseases. However, relatively little is currently understood regarding the physiologic roles of individual PKC isozymes or their substrates for phosphorylation in mitochondria. Recent advances in mitochondrial localization of PKC isozymes and methods of PKC isozyme-selective inhibition have made possible a more focused pursuit of these relationships. Studies of PKC isozyme involvement in areas such as mitochondrial ROS production, antioxidant defense, energetics, and apoptosis are now possible and hold the potential to provide promising pharmaceuticals for therapies against cardiovascular, diabetic, cancer and other diseases. The purpose of this review is to present the current state of knowledge illustrating a link between PKC isozymes, mitochondria and human disease. Novel strategies for PKC isozyme-selective inhibition will also be discussed with an emphasis on the rational targeting of mitochondrial PKC isozymes in research and clinical settings.
Keywords: Protein kinase C isozyme-selective inhibition, mitochondria, apoptosis, ROS, energetics, disease, antisense, pseudosubstrate, translocation inhibitors
Current Enzyme Inhibition
Title: Modulation of Mitochondrial Protein Kinase C Isozymes: A New Therapeutic Frontier?
Volume: 3 Issue: 2
Author(s): Tiffany Nguyen, Mourad Ogbi, Dehuang Guo and John A. Johnson
Affiliation:
Keywords: Protein kinase C isozyme-selective inhibition, mitochondria, apoptosis, ROS, energetics, disease, antisense, pseudosubstrate, translocation inhibitors
Abstract: Alterations in protein kinase C (PKC) isozymes and mitochondrial functions such as oxidative phosphorylation (OXPHOS) and apoptosis have each been implicated in human diseases. However, relatively little is currently understood regarding the physiologic roles of individual PKC isozymes or their substrates for phosphorylation in mitochondria. Recent advances in mitochondrial localization of PKC isozymes and methods of PKC isozyme-selective inhibition have made possible a more focused pursuit of these relationships. Studies of PKC isozyme involvement in areas such as mitochondrial ROS production, antioxidant defense, energetics, and apoptosis are now possible and hold the potential to provide promising pharmaceuticals for therapies against cardiovascular, diabetic, cancer and other diseases. The purpose of this review is to present the current state of knowledge illustrating a link between PKC isozymes, mitochondria and human disease. Novel strategies for PKC isozyme-selective inhibition will also be discussed with an emphasis on the rational targeting of mitochondrial PKC isozymes in research and clinical settings.
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Cite this article as:
Nguyen Tiffany, Ogbi Mourad, Guo Dehuang and Johnson A. John, Modulation of Mitochondrial Protein Kinase C Isozymes: A New Therapeutic Frontier?, Current Enzyme Inhibition 2007; 3 (2) . https://dx.doi.org/10.2174/157340807780598396
DOI https://dx.doi.org/10.2174/157340807780598396 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
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