Hypothermia Prevents the Ischemia‐Induced Translocation and Inhibition of Protein Kinase C in the Rat Striatum

Cardell, Monika; Boris-Möller, Fredrik; Wieloch, Tadeusz

doi:10.1111/j.1471-4159.1991.tb06387.x

Cited by 138 publications

(41 citation statements)

References 28 publications

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“…18 ' 19 However, lowered temperature, as examined, lacked the effect on the PLD activity decrease (Fig 4). One possible explanation is that PLD plays little role in neuronal injury in ischemia; however, the lack of hypothermic effect is explainable on the assumption that hypothermic condition may not completely protect against damage to the brain during ischemia and that the decrease in PLD activity may be caused by only slight ischemic damage in the hypothermic condition because of susceptibility of PLD to ischemia.…”

Section: Discussionmentioning

confidence: 99%

Brain ischemia decreases phosphatidylcholine-phospholipase D but not phosphatidylinositol-phospholipase C in rats.

Nishida

Emoto

Shimizu

et al. 1994

Stroke

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Background and Purpose Phosphatidylcholine (PC)-phospholipase D (PLD) is an important intracellular signaling pathway in response to a variety of agonists, but little is known about the effects of brain ischemia on the PC-PLD system. We thus have examined the effects of global cerebral ischemia on PLD in rats.Methods We have examined the effects of global ischemia (decapitation or four-vessel occlusion) on PLD and PLC activity in the membrane fraction of rat brains. We measured the PLD and PLC activity in detergent-mixed micelle assay systems using 3 H-labeled exogenous substrate. Results The results demonstrate that basal PLD activity showed a gradual decrease with increased duration (5 to 30 minutes) of ischemia by decapitation in the hippocampus; after 30 minutes of ischemia, PLD activity was significantly decreased compared with the control. Lineweaver-Burk plots showed that the apparent V max value of PLD in ischemia was one half of that in the control without changes in K m value.

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Section: Discussionmentioning

confidence: 99%

Brain ischemia decreases phosphatidylcholine-phospholipase D but not phosphatidylinositol-phospholipase C in rats.

Nishida

Emoto

Shimizu

et al. 1994

Stroke

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“…Intraischemic hypothermia delays or attenuates both ATP depletion (Ibayashi et al, 2000;Sutton et al, 1991;Welsh et al, 1990) and anoxic depolarization (Bart et al, 1998;Nakashima and Todd, 1996;Takeda et al, 2003), it also blocks glutamate release (Busto et al, 1989b;Patel et al, 1994;Winfree et al, 1996), suppresses inflammation (Kawai et al, 2000;Wang et al, 2002), maintains the integrity of the BBB (Dietrich et al, 1990;Huang et al, 1999;Kawanishi, 2003), reduces free radical production , inhibits protein kinase C translocation (Cardell et al, 1991;Shimohata et al, 2007a, b;Tohyama et al, 1998), inhibits matrix metalloproteinase expression (Hamann et al, 2004), and blocks both necrosis and apoptosis. Intraischemic hypothermia also preserves the base-excision repair pathway, which repairs oxidative damage (Luo et al, 2007).…”

Section: The Ostensible Pan-inhibitive Effects Of Hypothermiamentioning

confidence: 99%

General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage

Zhao

Steinberg

Sapolsky

2007

J Cereb Blood Flow Metab

156

135

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Mild or moderate hypothermia is generally thought to block all changes in signaling events that are detrimental to ischemic brain, including ATP depletion, glutamate release, Ca 2 + mobilization, anoxic depolarization, free radical generation, inflammation, blood-brain barrier permeability, necrotic, and apoptotic pathways. However, the effects and mechanisms of hypothermia are, in fact, variable. We emphasize that, even in the laboratory, hypothermic protection is limited. In certain models of permanent focal ischemia, hypothermia may not protect at all. In cases where hypothermia reduces infarct, some studies have overemphasized its ability to maintain cerebral blood flow and ATP levels, and to prevent anoxic depolarization, glutamate release during ischemia. Instead, hypothermia may protect against ischemia by regulating cascades that occur after reperfusion, including blood-brain barrier permeability and the changes in gene and protein expressions associated with necrotic and apoptotic pathways. Hypothermia not only blocks multiple damaging cascades after stroke, but also selectively upregulates some protective genes. However, most of these mechanisms are addressed in models with intraischemic hypothermia; much less information is available in models with postischemic hypothermia. Moreover, although it has been confirmed that mild hypothermia is clinically feasible for acute focal stroke treatment, no definite beneficial effect has been reported yet. This lack of clinical protection may result from suboptimal criteria for patient entrance into clinical trials. To facilitate clinical translation, future efforts in the laboratory should focus more on the protective mechanisms of postischemic hypothermia, as well as on the effects of sex, age and rewarming during reperfusion on hypothermic protection.

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“…In addition, substances that diminish PKC translocation to the cell membranes are neuroprotective (Karpiak et al, 1990). Intraischemic neuroprotective hypothermia (Boris Moller et al, 1989;Busto et al, 1987) also prevents the translocation of PKC (Busto et al, 1994;Cardell et al, 1991). The translocation of PKC-␥ to membranes, which is also accompanied by a net and transient increase in its activity (DomanskaJanik, 1996), seems to cause pathological cell signaling and may contribute to ischemic cell death.…”

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confidence: 99%

Protein Kinase C-γ and Calcium/Calmodulin-Dependent Protein Kinase II-α Are Persistently Translocated to Cell Membranes of the Rat Brain during and after Middle Cerebral Artery Occlusion

Matsumoto

Shamloo²,

Matsumoto

et al. 2004

J Cereb Blood Flow Metab

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Summary:The levels of protein kinase C-␥ (PKC-␥ ) and the calcium/calmodulin-dependent kinase II-␣ (CaMKII-␣ ) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the penumbra, PKC␥ decreased in S3 without any significant increases in P2 and P3. Total PKC-␥ also decreased in the penumbra but not in the ischemic core, suggesting that the protein is degraded by an energy-dependent mechanism, possibly by the 26S proteasome. The CaMKII-␣ levels increased in P2 but not P3 during ischemia and reperfusion in all ischemic regions, particularly in the ischemic core. Concomitantly, the levels in S3 decreased by 20% to 40% in the penumbra and by approximately 80% in the ischemic core. There were no changes in the total levels of CaMKII-␣ during MCAO. The authors conclude that during and after ischemia, PKC and CaMKII-␣ are translocated to the cell membranes, particularly synaptic membranes, where they may modulate cellular function, such as neurotransmission, and also affect cell survival. Drugs preventing PKC and/or CaMKII-␣ translocation may prove beneficial against ischemic cell death.

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Hypothermia Prevents the Ischemia‐Induced Translocation and Inhibition of Protein Kinase C in the Rat Striatum

Cited by 138 publications

References 28 publications

Brain ischemia decreases phosphatidylcholine-phospholipase D but not phosphatidylinositol-phospholipase C in rats.

Brain ischemia decreases phosphatidylcholine-phospholipase D but not phosphatidylinositol-phospholipase C in rats.

General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage

Protein Kinase C-γ and Calcium/Calmodulin-Dependent Protein Kinase II-α Are Persistently Translocated to Cell Membranes of the Rat Brain during and after Middle Cerebral Artery Occlusion

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