Isoflurane Inhibits Protein Kinase Cγ and Calcium/Calmodulin Dependent Protein Kinase II-α Translocation to Synaptic Membranes in Ischemic Mice Brains

Matsumoto, Shohei; Murozono, Michihiro; Nagaoka, Daisuke; Matsuoka, Satomi; Takeda, Akihiro; Narita, Hideyuki; Watanabe, Sekiko; Isshiki, Atsushi; Watanabe, Yasuo

doi:10.1007/s11064-008-9727-4

Cited by 10 publications

(7 citation statements)

References 38 publications

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“…The reasons for these different findings are not known. However, consistent with our findings, it has been proposed in a recent study that inhibition of CaMKII trafficking to the plasma membrane, a possible activation process for CaMKII, is a mechanism for isoflurane-induced neuroprotection (Matsumoto et al, 2008). Interestingly, there is no report on the role of IP3 receptor-calcium-CaMKII pathway in isoflurane postconditioning-induced neuroprotection.…”

Section: Discussionsupporting

confidence: 93%

Isoflurane preconditioning and postconditioning in rat hippocampal neurons

McMurtrey

Zuo

2010

Brain Research

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The volatile anesthetic isoflurane is capable of inducing preconditioning and postconditioning effects in the brain. However, the mechanisms for these neuroprotective effects are not fully understood. Here, we showed that rat hippocampal neuronal cultures exposed to 2% isoflurane for 30 min at 24 h before a 1-h oxygen-glucose deprivation (OGD) and a 24-h simulated reperfusion had a reduced lactate dehydrogenase release. Similarly, this OGD and simulated reperfusion-induced lactate dehydrogenase release was attenuated by exposing the neuronal cultures to 2% isoflurane for 1 h at various times after the onset of the simulated reperfusion (isoflurane postconditioning). The combination of isoflurane preconditioning and postconditioning induced a better neuroprotection than either alone. Inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII), inhibition of N-methyl D-aspartate (NMDA) receptors, or activation of adenosine A2A receptors resulted in reduction of the OGD and simulated reperfusion-induced cell injury. The combination of CaMKII inhibition and isoflurane preconditioning or postconditioning did not provide better protection than CaMKII inhibition, isoflurane preconditioning, or isoflurane postconditioning alone. The combination of NMDA receptor inhibition and isoflurane postconditioning was not better than NMDA receptor inhibition or isoflurane postconditioning alone for neuroprotection. However, the combination of adenosine A2A receptor activation with either isoflurane preconditioning or isoflurane postconditioning induced a better neuroprotective effect than adenosine A2A receptor activation, isoflurane preconditioning, or isoflurane postconditioning alone. The combination of NMDA receptor inhibition and isoflurane preconditioning caused a better neuroprotective effect than NMDA receptor inhibition or isoflurane preconditioning alone. These results suggest that isoflurane preconditioning- and postconditioning-induced neuroprotection can be additive. Isoflurane preconditioning and isoflurane postconditioning may involve CaMKII inhibition, but may not involve adenosine A2A receptor activation. Inhibition of NMDA receptors may mediate the effects of isoflurane postconditioning, but not isoflurane preconditioning.

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Section: Discussionsupporting

confidence: 93%

Isoflurane preconditioning and postconditioning in rat hippocampal neurons

McMurtrey

Zuo

2010

Brain Research

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“…Within the brain, PKCγ levels are most abundant in the cerebellum, hippocampus and cerebral cortex, where notable neuronal plasticity occurs (33,34). Recently, Matsumoto et al demonstrated that the PKCγ expression was significantly increased following TBI in rats (35). Nevertheless, to the best of our knowledge, no studies have examined the potential for BBG to regulate the expression of PKCγ in neurons in an animal model.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of brilliant blue G on the brain following traumatic brain injury in rats

Wang

Cui

et al. 2015

Molecular Medicine Reports

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The P2X7 inhibitor, brilliant blue G (BBG), has been reported as a neuroprotective drug against a variety of disorders, including neuropathic pain and brain ischemia. Currently, no studies have examined the potential for BBG to provide neuroprotection in animal models of TBI. The aim of the present study was to investigate the neuroprotective effect of BBG on TBI and to determine the underlying mechanisms. The rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device, and then divided randomly into three groups: the sham-operated, BBG treatment and vehicle groups. In the BBG treatment group, 50 mg/kg brilliant blue G (BBG; 100% pure), a highly specific and clinically useful P2X7 antagonist, was administered via the tail vein 15 min prior to or up to 8 h following TBI. The co-localization of NeuN and protein kinase Cγ (PKCγ) was followed with immunofluorescent staining. The expression of P2X7, PKCγ and inflammatory cytokines was identified by western blot analysis. Wet-dry weight method was used to evaluate brain edema, and motor function outcome was examined using the neurological severity score. The present study demonstrated that the administration of BBG attenuated TBI-induced cerebral edema and the associated motor deficits. Following trauma, BBG treatment significantly reduced the levels of PKCγ and interleukin-1β in the cortex. The results provide in vivo evidence that BBG exerted neuroprotective effects by attenuating brain edema and improving neurological functions via reducing PKCγ and interleukin-1β levels following TBI.

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“…Down-regulation of cPKCc membrane translocation by its inhibitor can inhibit the increment in lactate dehydrogenase (LDH) leakage induced by 20-min. OGD treatment and decrease the decapitation-induced ischaemic brain injury of C57Bl/6J mice [5,11]. The different effects of cPKCc may be attributable to the use of different species, models, protocols, measured end-points and inhibitors.…”

Section: Introductionmentioning

confidence: 99%

cPKCγ‐mediated down‐regulation ofUCHL1 alleviates ischaemic neuronal injuries by decreasing autophagyviaERK‐mTORpathway

Zhang

Han

Wang

et al. 2017

J Cellular Molecular Medi

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Stroke is one of the leading causes of death in the world, but its underlying mechanisms remain unclear. Both conventional protein kinase C (cPKC)γ and ubiquitin C‐terminal hydrolase L1 (UCHL1) are neuron‐specific proteins. In the models of 1‐hr middle cerebral artery occlusion (MCAO)/24‐hr reperfusion in mice and 1‐hr oxygen–glucose deprivation (OGD)/24‐hr reoxygenation in cortical neurons, we found that cPKCγ gene knockout remarkably aggravated ischaemic injuries and simultaneously increased the levels of cleaved (Cl)‐caspase‐3 and LC3‐I proteolysis product LC3‐II, and the ratio of TUNEL‐positive cells to total neurons. Moreover, cPKCγ gene knockout could increase UCHL1 protein expression via elevating its mRNA level regulated by the nuclear factor κB inhibitor alpha (IκB‐α)/nuclear factor κB (NF‐κB) pathway in cortical neurons. Both inhibitor and shRNA of UCHL1 significantly reduced the ratio of LC3‐II/total LC3, which contributed to neuronal survival after ischaemic stroke, but did not alter the level of Cl‐caspase‐3. In addition, UCHL1 shRNA reversed the effect of cPKCγ on the phosphorylation levels of mTOR and ERK rather than that of AMPK and GSK‐3β. In conclusion, our results suggest that cPKCγ activation alleviates ischaemic injuries of mice and cortical neurons through inhibiting UCHL1 expression, which may negatively regulate autophagy through ERK‐mTOR pathway.

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Isoflurane Inhibits Protein Kinase Cγ and Calcium/Calmodulin Dependent Protein Kinase II-α Translocation to Synaptic Membranes in Ischemic Mice Brains

Cited by 10 publications

References 38 publications

Isoflurane preconditioning and postconditioning in rat hippocampal neurons

Isoflurane preconditioning and postconditioning in rat hippocampal neurons

Neuroprotective effects of brilliant blue G on the brain following traumatic brain injury in rats

cPKCγ‐mediated down‐regulation ofUCHL1 alleviates ischaemic neuronal injuries by decreasing autophagyviaERK‐mTORpathway

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