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

Nishida, Akira; Emoto, Katsuya; Shimizu, Masami; Uozumi, Touru; Yamawaki, Shigeto

doi:10.1161/01.str.25.6.1247

Cited by 23 publications

(10 citation statements)

References 27 publications

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“…The above results are in agreement with the report that brain PLD activity was significantly decreased in the hippocampus after ischemia by four-vessel occlusion [18]. It has also been reported that PLD1 activity and mRNA level were down-regulated during apoptosis [17].…”

Section: Discussionsupporting

confidence: 93%

“…Consequently, it leads to the swelling of the nerve cell and its internal organelles in the acute process of necrosis [9,14,21], and phosphatidylserine (PS) translocation to the exterior surface of the cell in apoptosis [2,10,29,30,32]. Therefore, it is hypothesized that PLD malfunction could be involved in apoptosis, since ischemia has been shown to decrease PLD activity [18]. Currently, it is unclear whether ischemia induces decrease of PLD activity is due either to the release of endogenous enzyme inhibitors or the reduction of PLD2 mRNA expression.…”

Section: Introductionmentioning

confidence: 99%

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Down-regulation of Phospholipase D2 mRNA in Neonatal Rat Brainstem and Cerebellum after Hypoxia-Ischemia

2006

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Phospholipase D (PLD) and phosphatidylcholine (PC) were implicated in apoptosis and cancer. However, direct evidence on the role of PLD in the cause of apoptosis remains obscure. It was recently reported that apoptosis and necrosis could be induced in the cerebellum and brainstem after focal cerebral hypoxic-ischemic (HI) injury. It was found that apoptosis could be enhanced by farnesol inhibition of PLD signal transduction. Whereas it was shown that highly invasive cancer cell line depends on PLD activity for survival when deprived of serum growth factors. Based on these reports, it is postulated that apoptosis in the cerebellum and brainstem induced after focal cerebral HI treatment may be caused by faulty PLD expression. This is consistent with a report that PLD1 activity and mRNA levels were down-regulated during apoptosis. To test this hypothesis, Northern blotting was used to examine PLD2 mRNA expression after focal cerebral HI. The results show that both PLD2 mRNA 10.8 and 3.9 kb transcripts were significantly decreased by as much as 37% in the brainstem and cerebellum areas 3 h after HI compared to the control, concur with previous report of decreasing PLD activity after ischemia. These PLD2 transcripts, however, were not significantly different from the control 3 days after HI, indicating that the decrease in PLD2 transcription after HI maybe a transient phenomenon. This is the first report to show that the loss of membrane integrity resulting from deprivation of energy and growth factors after HI could cause decrease in PLD2 transcription that promotes apoptosis. The hypothetic role of PLD2 and the mechanism leading to apoptosis remains to be further elucidated.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Down-regulation of Phospholipase D2 mRNA in Neonatal Rat Brainstem and Cerebellum after Hypoxia-Ischemia

2006

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“…in vivo may activate various calcium-regulated enzymes including phospholipases (Nishida et al ., 1994), kinases (Dash et al ., 1994), and phosphatases (Morioka et al ., 1992 ;Yamasaki et al, 1992) . The relative contributions of these enzymes to neuronal cytoskeletal damage are not yet known .…”

mentioning

confidence: 99%

μ‐Calpain Activation and Calpain‐Mediated Cytoskeletal Proteolysis Following Traumatic Brain Injury

Kampfl

Posmantur

Nixon

et al. 1996

Journal of Neurochemistry

145

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Increasing evidence suggests that excessive activation of the calcium‐activated neutral protease μ‐calpain could play a major role in calcium‐mediated neuronal degeneration after acute brain injuries. To further investigate the changes of the in vivo activity of μ‐calpain after unilateral cortical impact injury in vivo, the ratio of the 76‐kDa activated isoform of μ‐calpain to its 80‐kDa precursor was measured by western blotting. This μ‐calpain activation ratio increased to threefold in the pellet of cortical samples ipsilateral to the injury site at 15 min, 1 h, 3 h, and 6 h after injury and returned to control levels at 24–48 h after injury. We also investigated the effect of μ‐calpain activation on proteolysis of the neuronal cytoskeletal protein α‐spectrin. Immunoreactivity for α‐spectrin breakdown products was detectable within 15 min after injury in cortical samples ipsilateral to the injury site. The levels of α‐spectrin breakdown products increased in a biphasic manner, with a large increase between 15 min and 6 h after injury, followed by a smaller increase between 6 and 24 h after the insult. No further accumulation of α‐spectrin breakdown products was observed between 24 and 48 h after injury. Histopathological examinations using hematoxylin and eosin staining demonstrated dark, shrunken neurons within 15 min after traumatic brain injury. No evidence of μ‐calpain autolysis, calpain‐mediated α‐spectrin degradation, or hematoxylin and eosin neuronal pathology was detected in the contralateral cortex. Although μ‐calpain autolysis and cytoskeletal proteolysis occurred concurrently with early morphological alterations, evidence of calpain‐mediated proteolysis preceded the full expression of evolutionary histopathological changes. Our results indicate that rapid and persistent μ‐calpain activation plays an important role in cortical neuronal degeneration after traumatic brain injury. Our data also suggest that specific inhibitors of calpain could be potential therapeutic agents for the treatment of traumatic brain injury in vivo.

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“…For the first time, our results have demonstrated that the expression of PLD1 is markedly upregulated in reactive astrocytes in the hippocampus after transient forebrain ischemia. By contrast, Nishida et al (1994) reported that global brain ischemia decreases PLD activity in the membrane fraction of rat brains. The conflict in these results may have arisen from the fact that the latter results were obtained after 30 min of ischemia without reperfusion, whereas our results were obtained in rats that were allowed to survive for at least 1 day after reperfusion.…”

Section: Discussionmentioning

confidence: 90%

Upregulation of phospholipase D in astrocytes in response to transient forebrain ischemia

Lee

Kim

Min

et al. 2000

Glia

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

Cited by 23 publications

References 27 publications

Down-regulation of Phospholipase D2 mRNA in Neonatal Rat Brainstem and Cerebellum after Hypoxia-Ischemia

Down-regulation of Phospholipase D2 mRNA in Neonatal Rat Brainstem and Cerebellum after Hypoxia-Ischemia

μ‐Calpain Activation and Calpain‐Mediated Cytoskeletal Proteolysis Following Traumatic Brain Injury

Upregulation of phospholipase D in astrocytes in response to transient forebrain ischemia

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