Protein Kinase C Delta Cleavage Initiates an Aberrant Signal Transduction Pathway after Cardiac Arrest and Oxygen Glucose Deprivation

Raval, Ami P.; Dave, Kunjan R.; Prado, Ricardo; Katz, Laurence M.; Busto, Raul; Sick, Thomas J.; Ginsberg, Myron D.; Mochly‐Rosen, Daria; Pérez-Pinzón, Miguel A.

doi:10.1038/sj.jcbfm.9600071

Cited by 59 publications

(56 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also measured proteolytic activation of PKC␦, a substrate for caspase-3 (63). The activation of PKC␦ has been previously demonstrated to play a key role in the execution of apoptosis in various cell types, including neuronal cells (63,64). As shown in Fig.…”

Section: Gtpp and Egcg Protect Pc12 Cells From Ogd/r-induced Cell Deamentioning

confidence: 91%

Green Tea Polyphenols Precondition against Cell Death Induced by Oxygen-Glucose Deprivation via Stimulation of Laminin Receptor, Generation of Reactive Oxygen Species, and Activation of Protein Kinase Cϵ

Gundimeda

McNeill

Elhiani

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Gtpp and Egcg Protect Pc12 Cells From Ogd/r-induced Cell Deamentioning

confidence: 91%

Green Tea Polyphenols Precondition against Cell Death Induced by Oxygen-Glucose Deprivation via Stimulation of Laminin Receptor, Generation of Reactive Oxygen Species, and Activation of Protein Kinase Cϵ

Gundimeda

McNeill

Elhiani

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…In our previous study, we showed that ePKC mediated ischemic PC neuroprotection in vitro (Bright et al, 2004;Choi et al, 2006;Kim et al, 2007;Lange-Asschenfeldt et al, 2004;Perez-Pinzon et al, 2005;Raval et al, 2003Raval et al, , 2005. We also showed that ePKC activation induced phosphorylation of ERK1/2, which indicated activation of ERK1/2 and which was downstream of ePKC activation (Kim et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Preconditioning Mediated by Sublethal Oxygen—Glucose Deprivation-Induced Cyclooxygenase-2 Expression via the Signal Transducers and Activators of Transcription 3 Phosphorylation

Kim

Raval

Pérez-Pinzón

2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (ePKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen-glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or ePKC activation. Inhibition of either ePKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after ePKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance.

show abstract

“…Delta protein kinase C cleavage has also been shown in neuronal cells after exposure to neurotoxic agents (Anantharam et al, 2002). When CF-dPKC is overexpressed in cultured cells, it rapidly induces apoptosis (Raval et al, 2005).…”

Section: Proteolytic Cleavage Of Delta Protein Kinase C After Stroke mentioning

confidence: 99%

Suppression of δPKC Activation after Focal Cerebral Ischemia Contributes to the Protective Effect of Hypothermia

Shimohata

Zhao

Sung

et al. 2007

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

Mild hypothermia is a robust neuroprotective treatment for stroke. Understanding the mechanisms underlying hypothermia's benefits will lead to more effective treatments to prevent stroke damage. Delta protein kinase C (dPKC) is a kinase that has been strongly implicated in executing ischemic damage. We investigated the effects of hypothermia on dPKC activation, as determined by its subcellular translocation, proteolytic cleavage, and phosphorylation in a focal cerebral ischemia model. The amount of constitutively activated C-terminal catalytic fragment of dPKC (CF-dPKC) increased after stroke. Both hypothermia (301C) and the caspase-3-specific inhibitor, Z-DQMD-FMK, blocked the accumulation of activated dPKC in the penumbra. Other hallmarks of dPKC activation, its translocation to the mitochondria, and nucleus were observed in the penumbra as early as 10 mins after reperfusion. These events were blocked by hypothermia. Hypothermia also blocked CF-dPKC increases in the mitochondria and nuclei. Conversely, a specific dPKC activator, wdRACK, decreased the neuroprotective effect of hypothermia. Finally, dPKC activity may lead to mitochondrial injury and cytochrome c release, as the timing of cytochrome c release corresponded to the time course of dPKC translocation. Both cytochrome c release and dPKC translocation were blocked by hypothermia. In conclusion, hypothermia protects against ischemic damage in part by suppressing dPKC activation after stroke.

show abstract

Protein Kinase C Delta Cleavage Initiates an Aberrant Signal Transduction Pathway after Cardiac Arrest and Oxygen Glucose Deprivation

Cited by 59 publications

References 47 publications

Green Tea Polyphenols Precondition against Cell Death Induced by Oxygen-Glucose Deprivation via Stimulation of Laminin Receptor, Generation of Reactive Oxygen Species, and Activation of Protein Kinase Cϵ

Green Tea Polyphenols Precondition against Cell Death Induced by Oxygen-Glucose Deprivation via Stimulation of Laminin Receptor, Generation of Reactive Oxygen Species, and Activation of Protein Kinase Cϵ

Preconditioning Mediated by Sublethal Oxygen—Glucose Deprivation-Induced Cyclooxygenase-2 Expression via the Signal Transducers and Activators of Transcription 3 Phosphorylation

Suppression of δPKC Activation after Focal Cerebral Ischemia Contributes to the Protective Effect of Hypothermia

Contact Info

Product

Resources

About