Cell Signaling through Protein Kinase C Oxidation and Activation

Cosentino-Gomes, Daniela; Rocco-Machado, Nathália; Meyer‐Fernandes, José Roberto

doi:10.3390/ijms130910697

Cited by 214 publications

(170 citation statements)

References 182 publications

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“…ROS are very important intracellular signaling molecules, which are associated with PKC activation (Otani, 2004;Cosentino-Gomes et al, 2012) in IP, whereas the opening of MitoK ATP channels can cause the release of ROS (Eaton et al, 2005;Costa and Garlid, 2008;Gordon et al, 2009;Hirata et al, 2011;Jin et al, 2012). Our findings also show that scavenging the ROS produced after the MitoK ATP channels were opened could inhibit the translocation and activation of PKCε.…”

Section: Discussionsupporting

confidence: 57%

Effect of mitochondrial ATP-sensitive potassium channel opening on the translocation of protein kinase C epsilon in adult rat ventricular myocytes

Yang

Long

et al. 2014

Genet. Mol. Res.

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ABSTRACT. This study aimed to investigate the effects of mitochondrial ATP-sensitive potassium (MitoK ATP ) channel opening on the translocation of protein kinase C epsilon (PKCε). In addition, we aimed to determine the relationship between PKCε translocation and the production of reactive oxygen species (ROS). PKCε protein expression in cultured adult rat ventricular myocytes was investigated by immunofluorescence and Western blotting. Diazoxide (DZ), a selective MitoK ATP channel activator, caused a significant translocation to myofibrillar-like structures in cultured adult rat ventricular myocytes. N-2-Mercaptopropionylglycine, a free radical scavenger, could partially inhibit the translocation of PKCε induced by DZ. By contrast, chelerythrine, a selective PKC inhibitor, could completely block the translocation of PKCε induced by DZ. The opening of MitoK ATP channels might activate and cause PKCε to translocate into myofibrillar-like structures. PKCε activation occurred downstream of the MitoK ATP channel, possibly as a result of ROS production that 4517 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 4516-4522 (2014) MitoK ATP channels and PKCε translocation occurred after the MitoK ATP channels opened.

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Section: Discussionsupporting

confidence: 57%

Effect of mitochondrial ATP-sensitive potassium channel opening on the translocation of protein kinase C epsilon in adult rat ventricular myocytes

Yang

Long

et al. 2014

Genet. Mol. Res.

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“…Interestingly, there has been increasing evidence that many PKC isoforms can be activated by cellular oxidants (e.g., superoxide and H 2 O 2 ) independently of either Ca 21 or lipid mediators, such as DAG (Gopalakrishna and Anderson, 1989;Knapp and Klann, 2000;Cosentino-Gomes et al, 2012). We hypothesized that mitochondrial ROS induces airway nociceptor hyperexcitability to a,b-mATP via activation of protein kinase C. For these studies, we used a selective PKC inhibitor called bisindolylmaleimide I (BIM I; also known as GF 109203X and Gö 6850) and its inactive analog BIM V (also known as Ro 31-6045).…”

Section: Resultsmentioning

confidence: 99%

Sensory Nerve Terminal Mitochondrial Dysfunction Induces Hyperexcitability in Airway Nociceptors via Protein Kinase C

2014

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Airway sensory nerve excitability is a key determinant of respiratory disease-associated reflexes and sensations such as cough and dyspnea. Inflammatory signaling modulates mitochondrial function and produces reactive oxygen species (ROS). Peripheral terminals of sensory nerves are densely packed with mitochondria; thus, we hypothesized that mitochondrial modulation would alter neuronal excitability. We recorded action potential firing from the terminals of individual bronchopulmonary C-fibers using a mouse ex vivo lung-vagal ganglia preparation. C-fibers were characterized as nociceptors or non-nociceptors based upon conduction velocity and response to transient receptor potential (TRP) channel agonists. Antimycin A (mitochondrial complex III Q i site inhibitor) had no effect on the excitability of non-nociceptors. However, antimycin A increased excitability in nociceptive C-fibers, decreasing the mechanical threshold by 50% and increasing the action potential firing elicited by a P2X 2/3 agonist to 270% of control. Antimycin A-induced nociceptor hyperexcitability was independent of TRP ankyrin 1 or TRP vanilloid 1 channels. Blocking mitochondrial ATP production with oligomycin or myxothiazol had no effect on excitability. Antimycin A-induced hyperexcitability was dependent on mitochondrial ROS and was blocked by intracellular antioxidants. ROS are known to activate protein kinase C (PKC). Antimycin A-induced hyperexcitability was inhibited by the PKC inhibitor bisindolylmaleimide (BIM) I, but not by its inactive analog BIM V. In dissociated vagal neurons, antimycin A caused ROS-dependent PKC translocation to the membrane. Finally, H 2 O 2 also induced PKC-dependent nociceptive C-fiber hyperexcitability and PKC translocation. In conclusion, ROS evoked by mitochondrial dysfunction caused nociceptor hyperexcitability via the translocation and activation of PKC.

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“…This is a dangerous proposition given the autocatalytic nature of the lipid oxidation pathway and can be easily derailed by diminished HSD10 activity or abundance. In addition, HSD10 would create DAG ox , a product that can activate cell signaling pathways outside of the mitochondria, such as protein kinase C, a wellknown enzyme that blocks further effects of oxidative stress (Gopalakrishna and Jaken 2000;Cosentino-Gomes et al 2012). DAG ox is known to activate these pathways similarly and in some cases in greater magnitude than DAG (Kambayashi et al 2007;Takekoshi et al 2014).…”

Section: Hsd10 May Mediate CL Homeostasismentioning

confidence: 99%

Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases

Boynton

Shimkets

2015

Genes Dev.

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Myxococcus xanthus development requires CsgA, a member of the short-chain alcohol dehydrogenase (SCAD) family of proteins. We show that CsgA and SocA, a protein that can replace CsgA function in vivo, oxidize the 2 ′ -OH glycerol moiety on cardiolipin and phosphatidylglycerol to produce diacylglycerol (DAG), dihydroxyacetone, and orthophosphate. A lipid extract enriched in DAGs from wild-type cells initiates development and lipid body production in a csgA mutant to bypass the mutational block. This novel phospholipase C-like reaction is widespread. SCADs that prevent neurodegenerative disorders, such as Drosophila Sniffer and human HSD10, oxidize cardiolipin with similar kinetic parameters. HSD10 exhibits a strong preference for cardiolipin with oxidized fatty acids. This activity is inhibited in the presence of the amyloid β peptide. Three HSD10 variants associated with neurodegenerative disorders are inactive with cardiolipin. We suggest that HSD10 protects humans from reactive oxygen species by removing damaged cardiolipin before it induces apoptosis.

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Cell Signaling through Protein Kinase C Oxidation and Activation

Cited by 214 publications

References 182 publications

Effect of mitochondrial ATP-sensitive potassium channel opening on the translocation of protein kinase C epsilon in adult rat ventricular myocytes

Effect of mitochondrial ATP-sensitive potassium channel opening on the translocation of protein kinase C epsilon in adult rat ventricular myocytes

Sensory Nerve Terminal Mitochondrial Dysfunction Induces Hyperexcitability in Airway Nociceptors via Protein Kinase C

Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases

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