Changes in lipid metabolites and enzymes in rat brain due to ischemia and recirculation

Moto, Atsufumi; Hirashima, Yutaka; Endo, Shunro; Takaku, Akira

doi:10.1007/bf03160996

Cited by 11 publications

(4 citation statements)

References 31 publications

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“…Some studies showed a significant decrease in the content of brain phospholipids [8–10, 37], whereas other studies found no change [11, 13], even after 60 min of ischemia [12]. These contradictory findings suggest that ischemia alone is not sufficient to cause significant phospholipid alterations.…”

Section: Discussionmentioning

confidence: 99%

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation

et al. 2015

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Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30 min asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model. Following 30 min CA and CPB resuscitation, rats showed no brain function, moderately compromised heart function, and died within a few hours; typical outcomes of severe CA. However, we did not find any significant change in the content or composition of phospholipids in either tissue following 30 min CA or CA followed by CPB resuscitation. We found a moderate increase in lysophosphatidylinositol in both tissues, and a small increase in lysophosphatidylethanolamine and lysophosphatidylcholine only in brain tissue following CA. CPB resuscitation significantly decreased lysophosphatidylinositol but did not alter the other lyso species. These results indicate that a decrease in phospholipids is not a cause of brain damage in CA or a characteristic of brain ischemia. However, a significant increase in lysophosphatidylcholine and lysophosphatidylethanolamine found only in the brain with more damage suggests that impaired phospholipid metabolism may be correlated with the severity of ischemia in CA. In addition, the unique response of lysophosphatidylinositol suggests that phosphatidylinositol metabolism is highly sensitive to cellular conditions altered by ischemia and resuscitation.

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Section: Discussionmentioning

confidence: 99%

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation

et al. 2015

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“…Abnormal membrane breakdown and/or turnover has been implicated in several human brain disorders including Alzheimer's disease (2,3), cerebral ischemia (4,5), schizophrenia (6)(7)(8), and cerebellar ataxia (9,10). This has prompted some investigators to consider the use of inhibitors of membrane breakdown or stimulators of membrane synthesis as potential therapeutic agents in these diseases.…”

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confidence: 99%

Phospholipid biosynthetic enzymes in human brain

Ross

Moszczynska²,

Blusztajn

et al. 1997

Lipids

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Growing evidence suggests an involvement of brain membrane phospholipid metabolism in a variety of neurodegenerative and psychiatric conditions. This has prompted the use of drugs (e.g., CDPcholine) aimed at elevating the rate of neural membrane synthesis. However, no information is available regarding the human brain enzymes of phospholipid synthesis which these drugs affect. Thus, the objective of our study was to characterize the enzymes involved, in particular, whether differences existed in the relative affinity of substrates for the enzymes of phosphatidylethanolamine (PE) compared to those of phosphatidylcholine (PC) synthesis. The concentration of choline in rapidly frozen human brain biopsies ranged from 32-186 nmol/g tissue, a concentration similar to that determined previously for ethanolamine. Since human brain ethanolamine kinase possessed a much lower affinity for ethanolamine (Km = 460 microM) than choline kinase did for choline (Km = 17 microM), the activity of ethanolamine kinase in vivo may be more dependent on substrate availability than that of choline kinase. In addition, whereas ethanolamine kinase was inhibited by choline, and to a lesser extent by phosphocholine, choline kinase activity was unaffected by the presence of ethanolamine, or phosphoethanolamine, and only weakly inhibited by phosphocholine. Phosphoethanolamine cytidylyltransferase (PECT) and phosphocholine cytidylyltransferase (PCCT) also displayed dissimilar characteristics, with PECT and PCCT being located predominantly in the cytosolic and particulate fractions, respectively. Both PECT and PCCT exhibited a low affinity for CTP (Km approximately 1.2 mM), suggesting that the activities of these enzymes, and by implication, the rate of phospholipid synthesis, are highly dependent upon the cellular concentration of CTP. In conclusion our data indicate different regulatory properties of PE and PC synthesis in human brain, and suggest that the rate of PE synthesis may be more dependent upon substrate (ethanolamine) availability than that of PC synthesis.

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“…As described, prominent changes in lipids are reportedly accompanied in the ischemic brain, where a rapid decrease in phosphatidylinositol-4,5-bisphosphate (PIP 2 ) levels together with a parallel accumulation of diacylglycerol (DG) is observed (Kunievsky et al 1992). In addition, levels of PIP, PIP 2 , and DG approach plateau values after 10 min of ischemia ), a 30 min recirculation period after 15 min of ischemia engenders increases in PIP and PIP 2 , whereas levels of DG decrease promptly toward control values (Moto et al 1991;Yoshida et al 1986). Detailed analysis of lipid changes in distinct subcellular compartments should help to determine how DGK cytoplasmic translocation is implicated in DG metabolism, although it might be diYcult because of the rapid changes.…”

Section: Discussionmentioning

confidence: 91%

NMDA receptor-mediated Ca2+ influx triggers nucleocytoplasmic translocation of diacylglycerol kinase ζ under oxygen–glucose deprivation conditions, an in vitro model of ischemia, in rat hippocampal slices

Suzuki

Yamazaki

Hozumi

et al. 2012

Histochem Cell Biol

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Diacylglycerol kinase (DGK) plays a key role in pathophysiological cellular responses by regulating the levels of a lipid messenger diacylglycerol. Of DGK isozymes, DGKζ localizes to the nucleus in various cells such as neurons. We previously reported that DGKζ translocates from the nucleus to the cytoplasm in hippocampal CA1 pyramidal neurons after 20 min of transient forebrain ischemia. In this study, we examined the underlying mechanism of DGKζ translocation using hippocampal slices exposed to oxygen-glucose deprivation (OGD) to simulate an ischemic model of the brain. DGKζ-immunoreactivity gradually changed from the nucleus to the cytoplasm in CA1 pyramidal neurons after 20 min of OGD and was never detected in the nucleus after reoxygenation. Intriguingly, DGKζ was detected in the nucleus at 10 min OGD whereas the following 60 min reoxygenation induced complete cytoplasmic translocation of DGKζ. Morphometric analysis revealed that DGKζ cytoplasmic translocation correlated with nuclear shrinkage indicative of an early process of neuronal degeneration. The translocation under OGD conditions was blocked by NMDA receptor (NMDAR) inhibitor, and was induced by activation of NMDAR. Chelation of the extracellular Ca(2+) blocked the translocation under OGD conditions. These results show that DGKζ cytoplasmic translocation is triggered by activation of NMDAR with subsequent extracellular Ca(2+) influx. Furthermore, inhibition of PKC activity under OGD conditions led to nuclear retention of DGKζ in about one-third of the neurons, suggesting that PKC activity partially regulates DGKζ cytoplasmic translocation. These findings provide clues to guide further investigation of glutamate excitotoxicity mechanisms in hippocampal neurons.

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Changes in lipid metabolites and enzymes in rat brain due to ischemia and recirculation

Cited by 11 publications

References 31 publications

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation

Phospholipid biosynthetic enzymes in human brain

NMDA receptor-mediated Ca2+ influx triggers nucleocytoplasmic translocation of diacylglycerol kinase ζ under oxygen–glucose deprivation conditions, an in vitro model of ischemia, in rat hippocampal slices

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