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

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Abstract

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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References

  1. Beiharz EJ, Williams CE, Dragunow M, Sirimanne ES, Gluckman PD (1995) Mechanisms of delayed cell death following hypoxic-ischemic injury in immature rat: evidence for apoptosis during selective neuronal loss. Mol Brain Res 29:1–14

    Article  Google Scholar 

  2. Bratton DJ, Fadok VA, Richter DA, Kailey JM, Guthrie LA, Henson PM (1997) Appearance of phosphatidylserine on apoptotic cells requires calcium- mediated non-specific flip–flop and is enhanced by loss of the aminophospholipid translocase. J Biol Chem 272:26159–26165

    Article  PubMed  CAS  Google Scholar 

  3. Calvert JW, Zhou C, Nanda A, Zhang JH (2003) Effect of hyperbaric oxygen on apoptosis in neonatal hypoxia-ischemia rat model. J Appl Physiol 95(5):2072–2080

    PubMed  Google Scholar 

  4. Cohen MV, Liu Y, Liu GS, Wang P, Weinbrenner C, Cordis GA, Das DK, Downey JM (1996) Phospholipase D plays a role in ischemic preconditioning in rabbit heart. Circulation 94:1713–1718

    PubMed  CAS  Google Scholar 

  5. Cui Z, Houweling M (2002) Phosphatidylcholine and cell death. Biochim Biophys Acta 1585:87–96

    PubMed  CAS  Google Scholar 

  6. Dwyer BE, Nishimura RN, Powell CL, Mailheau SL (1987) Focal protein synthesis inhibition in a model of neonatal hypoxic-ischemic brain. Exp Neurol 95(2):277–289

    Article  PubMed  CAS  Google Scholar 

  7. Foster DA, Xu L (2003) Phospholipase D in cell proliferation and cancer. Mol Cancer Res 1:789–800

    PubMed  CAS  Google Scholar 

  8. Hanshaw RG, Smith BD (2005) New reagents for phosphatidylserine recognition and detection of apoptosis. Bioorg Med Chem 13(17):5035–5042

    Article  PubMed  CAS  Google Scholar 

  9. Hill IE, MacManus JP, Rasquinha I, Tuor UI (1995) DNA fragmentation indicative of apoptosis following unilateral cerebral hypoxia-ischemia in the neonatal rat. Brain Res 676:398–403

    Article  PubMed  CAS  Google Scholar 

  10. Kagan VE, Fabisiak JP, Shvedova AA, Tyurina YY, Schor NF, Kawai K (2000) Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis. FEBS Lett 477(1–2):1–7

    Article  PubMed  CAS  Google Scholar 

  11. Lafemina MJ, Sheldon RA, Ferriero DM (2006) Acute hypoxia-ischemia results in hydrogen peroxide accumulation in neonatal but not adult mouse brain. Pediatr Res 59(5):680–683

    Article  PubMed  CAS  Google Scholar 

  12. LeBlanc MH, Feng YZ, Fratkin JD (2000) TPCK pretreatment reduces hypoxic-ischemic brain injury in the newborn rat. Eur J Pharmacol 390:249–256

    Article  PubMed  CAS  Google Scholar 

  13. Levine S (1960) Anoxic-ischemic encephalopathy in rats. Am J Pathol 36:1–17

    PubMed  CAS  Google Scholar 

  14. Li Y, Powers C, Jiang N, Chopp M (1998) Intact, injured, necrotic and apoptotic cells after focal cerebral ischemia in the rat. J Neurol Sci 156:119–132

    Article  PubMed  CAS  Google Scholar 

  15. Li Z, Agellon LB, Allen TM, Umeda M, Jewell L, Mason A, Vance DE (2006) The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab 3(5):321–331

    Article  PubMed  CAS  Google Scholar 

  16. Miyamoto O, Auer RN (2000) Hypoxia, hyperoxia, ischemia, and brain necrosis. Neurology 54(2):362–371

    PubMed  CAS  Google Scholar 

  17. Nakashima S, Nozawa Y (1999) Possible role of phospholipase D in differentiation and apoptosis. Chem Phys Lipids 98(1–2):153–164

    Article  PubMed  CAS  Google Scholar 

  18. Nishida A, Emoto K, Shimizu M, Uozumi T, Yamawaki S (1994) Brain ischemia decreases phosphatidylcholine-phospholipase D but not phosphatidylinositol-phospholipase C in rats. Stroke 25:1247–1251

    PubMed  CAS  Google Scholar 

  19. Oshimoto H, Okamura S, Yoshida M, Mori M (2003) Increased activity and expression of phopholipase D2 in colorectal cancer. Oncol Res 14:31–37

    PubMed  CAS  Google Scholar 

  20. Peng JH, Rhodes PG (2000) Developmental expression of phopholipase D2 mRNA in rat brain. Int J Dev Neurosci 18:584–589

    Article  Google Scholar 

  21. Peng JH, Feng YZ, LeBlanc MH, Rhodes PG, Parker JC (2005) Apoptosis and necrosis in developing cerebellum and brainstem induced after focal cerebral hypoxia-ischemia injury. Dev Brain Res 156:87–92

    Article  CAS  Google Scholar 

  22. Ramos B, Salido GM, Campo ML, Claro E (2000) Inhibition of phosphatidylcholine synthesis precedes apoptosis induced by C2-ceramide: protection by exogenous phosphatidylcholine. Neuroreport 11(14):3103–3108

    PubMed  CAS  Google Scholar 

  23. Rauch C, Loughna PT (2005) Inward relocation of exogenous phosphatidylserine triggered by IGF-1 in non-apoptotic C2C12 cells is concentration dependent. Cell Biochem Funct 2005. 23(6):383–388

    Article  CAS  Google Scholar 

  24. Rice JE III, Vanucci RC, Brierley JB (1981) The influence of immunity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9(2):131–141

    Article  PubMed  Google Scholar 

  25. Saito S, Sakagami H, Kondo H (2000) Localization of mRNAs for phospholipase D types 1 and 2 in the brain of developing and mature rat. Dev Brain Res 120:41–47

    Article  CAS  Google Scholar 

  26. Sandra F, Degli Esposti M, Ndebele K, Gona P, knight D, Rosenquist M, Khostavi-Far R (2005) Tumor necrosis factor-related apoptosis-inducing ligand alters mitochondrial membrane lipids. Cancer Res 65(18):8286–8297

    Article  PubMed  CAS  Google Scholar 

  27. Taylor MM, MacDonald K, Morris AJ, McMaster CR (2005) Enhanced apoptosis through farnesol inhibition of phospholipase D signal transduction. FEBS J 272(19):5056–5063

    Article  PubMed  CAS  Google Scholar 

  28. Tuor UI, Manley JJ, Fyfe C (1999) Dexamethasone effects on cerebral protein synthesis prior to and following hypoxia-ischemia in immature rat. Brain Res Bull 48(1):61–64

    Article  PubMed  CAS  Google Scholar 

  29. Tyurina YY, Kawai K, Tyurin VA, Liu SX, Kagan VE, Fabisiak JP (2004) The plasma membrane is the site of selective phosphatidylserine oxidation during apoptosis: role of cytochrome C. Antioxid Redox Signal 6:209–225

    Article  PubMed  CAS  Google Scholar 

  30. Vabdeneijinde SM, Boshart L, Baehrecke EH, Dezeeuw CI, Reutelingsberger CPM, Vermeijkeers C (1998) Cell surface exposure of phosphatidylserine during apoptosis is phylogenetically conserved. Apoptosis 3:9–16

    Article  Google Scholar 

  31. Vannucci RC (1994) Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage. Pediatr Res 27:317–326

    Google Scholar 

  32. Walton M, Sirimanne E, Reutelingsberger C, Williams C, Gluckman P, Drafunow M (1997) Annexin labels apoptotic neurons following hypoxia- ischemia. Neuroreport 8:3871–3875

    PubMed  CAS  Google Scholar 

  33. Wright MM, Howe AG, Zaremberg V (2004) Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues. Biochem Cell Biol 82:18–26

    Article  PubMed  CAS  Google Scholar 

  34. Zheng Y, Rodrik V, Toschi A, Shi M, Hui L, Shen Y, Foster DA (2006) Phospholipase D couples survival and migration signals in stress response of human cancer cells. J Biol Chem 281(23):15862–15868

    Article  PubMed  CAS  Google Scholar 

  35. Zhu C, Wang X, Hagberg H, Blomgren K (2000) Correlation between caspase-3 activation and three different markers of DNA damage in neonatal cerebral hypoxia-ischemia. J Neurochem 75:819–829

    Article  PubMed  CAS  Google Scholar 

  36. Zovein A, Flowers-Ziegler J, Thamotharan S, Shin D, Sankar R, Nguyen K, Gambhir S, Devaskar SU (2004) Postnatal hypoxic-ischemic brain injury alters mechanisms mediating neuronal glucose transport. Am J Physiol Regul Integr Comp Physiol 286(2):R273–R282

    PubMed  CAS  Google Scholar 

  37. Zweigner J, Jackowski S, Smith SH, Van Der Merwe M, Weber JR, Tuomanen EI (2004) Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the brain. J Exp Med 200:99–106

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jeng-Hsiung F. Peng.

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Peng, JH.F., Feng, Y. & Rhodes, P.G. Down-regulation of Phospholipase D2 mRNA in Neonatal Rat Brainstem and Cerebellum after Hypoxia-Ischemia. Neurochem Res 31, 1191–1196 (2006). https://doi.org/10.1007/s11064-006-9171-2

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  • DOI: https://doi.org/10.1007/s11064-006-9171-2

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