Neuronal Protection and Preservation of Calcium/Calmodulin-Dependent Protein Kinase II and Protein Kinase C Activity by Dextrorphan Treatment in Global Ischemia

Aronowski, Jaroslaw; Waxham, M. Neal; Grotta, James C.

doi:10.1038/jcbfm.1993.72

Cited by 33 publications

(15 citation statements)

References 43 publications

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“…31 Previously, both PKC activity and an upstream activator of AMPK were shown to be important in preventing N-methyl-D-aspartate-induced neurodegeneration after cerebral ischemia. 32 More recently, studies in the heart have linked AMPK to the PKC family in ischemic protection, 20 but the involvement of a specific PKC isoform has not been determined. We showed here that PKCe activates AMPK in vitro and in vivo and that PKCe requires AMPK for neuroprotection against lethal OGD.…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C Epsilon Regulates Mitochondrial Pools of Nampt and NAD Following Resveratrol and Ischemic Preconditioning in the Rat Cortex

Morris-Blanco

Cohan

Neumann

et al. 2014

J Cereb Blood Flow Metab

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Preserving mitochondrial pools of nicotinamide adenine dinucleotide (NAD) or nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in NAD production, maintains mitochondrial function and confers neuroprotection after ischemic stress. However, the mechanisms involved in regulating mitochondrial-localized Nampt or NAD have not been defined. In this study, we investigated the roles of protein kinase C epsilon (PKCe) and AMP-activated protein kinase (AMPK) in regulating mitochondrial pools of Nampt and NAD after resveratrol or ischemic preconditioning (IPC) in the cortex and in primary neuronal-glial cortical cultures. Using the specific PKCe agonist ceRACK, we found that PKCe induced robust activation of AMPK in vitro and in vivo and that AMPK was required for PKCe-mediated ischemic neuroprotection. In purified mitochondrial fractions, PKCe enhanced Nampt levels in an AMPK-dependent manner and was required for increased mitochondrial Nampt after IPC or resveratrol treatment. Analysis of intrinsic NAD autofluorescence using two-photon microscopy revealed that PKCe modulated NAD in the mitochondrial fraction. Further assessments of mitochondrial NAD concentrations showed that PKCe has a key role in regulating the mitochondrial NAD þ / nicotinamide adenine dinucleotide reduced (NADH) ratio after IPC and resveratrol treatment in an AMPK-and Nampt-dependent manner. These findings indicate that PKCe is critical to increase or maintain mitochondrial Nampt and NAD after pathways of ischemic neuroprotection in the brain.

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Section: Discussionmentioning

confidence: 99%

Protein Kinase C Epsilon Regulates Mitochondrial Pools of Nampt and NAD Following Resveratrol and Ischemic Preconditioning in the Rat Cortex

Morris-Blanco

Cohan

Neumann

et al. 2014

J Cereb Blood Flow Metab

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“…The expression of the protein kinase C-binding protein Zeta was downregulated in rats treated with baicalin, which resulted in a decrease in the activity of protein kinase C (PKC). Aronowski et al [27] observed that the activity of PKC in the brain cortex and hippocampus decreased significantly after ischemia and this decrease could be alleviated by the pretreatment of the NMDA receptor antagonist. Further studies need to examine whether baicalin acts as an antagonist to the NMDA receptor.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile induced by oral administration of baicalin and gardenin after focal brain ischemia in rats1

Zhang

Wang

Zhang

et al. 2005

Acta Pharmacologica Sinica

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Aim: To investigate differential gene expression and the pharmacological mechanism of baicalin and gardenin in focal cerebral ischemia in rats with high-density cDNA microarray. Methods: Rat left middle cerebral arteries were occluded and treated with either baicalin or gardenin. The pharmacological effects were investigated using the difference in infarction areas before and after treatment, which were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Gene expression was demonstrated using a "Biostar40S" gene microarray. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the result of the selected genes. Results: Both baicalin and gardenin reduced the infarction areas in focal cerebral ischemia rats (P<0.05). The differential genes were 211, 177, and 70 (upregulated or downregulated) in the model group, baicalin, and gardenin treatment groups compared with the sham-operated group, respectively. Gene expression of RpL19 and Csnk2 underwent an approximately 1.9 and 2.1-fold increase, respectively, verified by semiquantitative RT-PCR, which was the same trend as the cDNA microarray. Conclusion: Differential gene expression with respect to the pharmacological effects of baicalin and gardenin on focal cerebral ischemia by cDNA microarray revealed a number of clues with respect to the therapeutic mechanisms of Chinese traditional medicine. In addition, the present study provided theoretical and experimental evidence that will aid future studies examining cerebral ischemia.

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“…Brain temperature in randomly selected animals in both experimental and control groups was recorded from corpus striatum contralateral to the side of ischemia, as previously described. 5 Additionally, temperature was monitored from the right temporalis muscle by means of a digital microprobe (Omega Engineering model 410B-T with 0.1°C resolution). The temporalis muscle temperature during ischemia and the first hour of reperfusion in the control and CNS-1102 groups at any time of the experiment was maintained between 36.2°C and 36.8°C with a heating lamp and wanning blanket.…”

Section: Production Of Ischemiamentioning

confidence: 99%

Graded bioassay for demonstration of brain rescue from experimental acute ischemia in rats.

Aronowski¹,

Ostrow²,

Samways³

et al. 1994

Stroke

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Background and Purpose This study explored the correlation between duration of focal ischemia and infarct volume in spontaneously hypertensive rats as a measure of outcome after neuroprotective intervention.Methods We used 2,3,5 -triphenyltetrazolium chloride staining to discriminate infarcted tissue and calculate infarct volume 24 hours after temporary tandem common carotid/ middle cerebral artery occlusion lasting 5 to 150 minutes. We used a graded bioassay described by logistic function and executed by computer program (ALLFIT) to evaluate changes in infarct volume after increasing durations of ischemia. The method allowed us to calculate the maximal infarct volume (VoL^) and the duration of ischemia before reperfusion producing half-maximal infarct size (T,,,). Hypothermia and the N-methyl-D-aspartate antagonist CNS-1102 begun after

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Neuronal Protection and Preservation of Calcium/Calmodulin-Dependent Protein Kinase II and Protein Kinase C Activity by Dextrorphan Treatment in Global Ischemia

Cited by 33 publications

References 43 publications

Protein Kinase C Epsilon Regulates Mitochondrial Pools of Nampt and NAD Following Resveratrol and Ischemic Preconditioning in the Rat Cortex

Protein Kinase C Epsilon Regulates Mitochondrial Pools of Nampt and NAD Following Resveratrol and Ischemic Preconditioning in the Rat Cortex

Gene expression profile induced by oral administration of baicalin and gardenin after focal brain ischemia in rats1

Graded bioassay for demonstration of brain rescue from experimental acute ischemia in rats.

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