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Modulation of AQP4 expression by the protein kinase C activator, phorbol myristate acetate, decreases ischemia-induced brain edema

  • Conference paper
Brain Edema XIII

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 96))

Summary

The protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), is known to interact with aquaporin-4 (AQP4), a waterselective transporting protein abundant in astrocytes and ependymal cells, that has been found to decrease osmotically-induced swelling. The purpose of this study was to examine whether PMA given at different time points following focal ischemia induced by middle cerebral artery occlusion (MCAO) reduces brain edema by AQP4 modulation.

Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or PMA infusion (230 µg/kg), starting either 60 minutes before, or 30 or 60 minutes after MCAO (each group n = 12). After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentrations. AQP4 expression was assessed by immunoblotting. Statistical analysis was performed by ANOVA followed by Tukey’s post hoc test.

PMA treatment significantly reduced brain water content concentration in the infarcted area when started before or 30 minutes postocclusion (p < 0.001, p = 0.022) and prevented the subsequent sodium shift (p < 0.05). Furthermore, PMA reduced ischemia-induced AQP4 up-regulation (p ≤ 0.05).

Attenuation of the ischemia-induced AQP4 up-regulation by PMA suggests that the reduction in brain edema formation following PMA treatment was at least in part mediated by AQP4 modulation.

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References

  1. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD (1996) Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 27: 1616–1623

    PubMed  CAS  Google Scholar 

  2. Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23: 137–149

    Article  PubMed  Google Scholar 

  3. Dijkhuizen RM, de Graaf RA, Tulleken KA, Nicolay K (1999) Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain. J Cereb Blood Flow Metab 19: 341–349

    Article  PubMed  CAS  Google Scholar 

  4. Gotoh O, Asano T, Koide T, Takakura K (1985) Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin. Stroke 16: 101–109

    PubMed  CAS  Google Scholar 

  5. Han Z, Wax MB, Patil RV (1998) Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation. J Biol Chem 273: 6001–6004

    Article  PubMed  CAS  Google Scholar 

  6. Han ZT, Tong YK, He LM, Zhang Y, Sun JZ, Wang TY, Zhang H, Cui YL, Newmark HL, Conney AH, Chang RL (1998) 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced increase in depressed white blood cell counts in patients treated with cytotoxic cancer chemotherapeutic drugs. Proc Natl Acad Sci USA 95: 5362–5365

    Article  PubMed  CAS  Google Scholar 

  7. Hussaini IM, Karns LR, Vinton G, Carpenter JE, Redpath GT, Sando JJ, VandenBerg SR (2000) Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific proliferative response in astrocytic tumor cells. J Biol Chem 275: 22348–22354

    Article  PubMed  CAS  Google Scholar 

  8. Kimelberg HK, Rutledge E, Goderie S, Charniga C (1995) Astrocytic swelling due to hypotonic or high K+ medium causes inhibition of glutamate and aspartate uptake and increases their release. J Cereb Blood Flow Metab 15: 409–416

    PubMed  CAS  Google Scholar 

  9. Lafuze JE, Baker MD, Oakes AL, Baehner RL (1987) Comparison of in vivo effects of intravenous infusion of N-formylmethionyl-leucyl-phenylalanine and phorbol myristate acetate in rabbits. Inflammation 11: 481–488

    Article  PubMed  CAS  Google Scholar 

  10. Loo DD, Zeuthen T, Chandy G, Wright EM (1996) Cotransport of water by the Na+/glucose cotransporter. Proc Natl Acad Sci USA 93: 13367–13370

    Article  PubMed  CAS  Google Scholar 

  11. Loubinoux I, Volk A, Borredon J, Guirimand S, Tiffon B, Seylaz J, Meric P (1997) Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging. Stroke 28: 419–427

    PubMed  CAS  Google Scholar 

  12. Manabe S, Lin YC, Takaoka M, Yamoto T, Yanai T, Yamashita K, Tarumi C, Matsunuma N, Masuda H (1992) Species difference in susceptibility to phorbol myristate acetate-induced leukopenia and lung injury: rat vs. dog. J Toxicol Sci 17: 211–223

    PubMed  CAS  Google Scholar 

  13. Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6: 159–163

    Article  PubMed  CAS  Google Scholar 

  14. Nakahama K, Nagano M, Fujioka A, Shinoda K, Sasaki H (1999) Effect of TPA on aquaporin 4 mRNA expression in cultured rat astrocytes. Glia 25: 240–246

    Article  PubMed  CAS  Google Scholar 

  15. Neely JD, Christensen BM, Nielsen S, Agre P (1999) Heterotetrameric composition of aquaporin-4 water channels. Biochemistry 38: 11156–11163

    Article  PubMed  CAS  Google Scholar 

  16. O’Flaherty JT, Cousart S, Lineberger AS, Bond E, Bass DA, DeChatelet LR, Leake ES, McCall CE (1980) Phorbol myristate acetate: in vivo effects upon neutrophils, platelets, and lung. Am J Pathol 101: 79–92

    PubMed  CAS  Google Scholar 

  17. Sato S, Umenishi F, Inamasu G, Sato M, Ishikawa M, Nishizawa M, Oizumi T (2000) Expression of water channel mRNA following cerebral ischemia. Acta Neurochir [Suppl] 76: 239–241

    CAS  Google Scholar 

  18. Strair RK, Schaar D, Goodell L, Aisner J, Chin KV, Eid J, Senzon R, Cui XX, Han ZT, Knox B, Rabson AB, Chang R, Conney A (2002) Administration of a phorbol ester to patients with hematological malignancies: preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate. Clin Cancer Res 8: 2512–2518

    PubMed  CAS  Google Scholar 

  19. Sun MC, Honey CR, Berk C, Wong NL, Tsui JK (2003) Regulation of aquaporin-4 in a traumatic brain injury model in rats. J Neurosurg 98: 565–569

    Article  PubMed  CAS  Google Scholar 

  20. Taniguchi M, Yamashita T, Kumura E, Tamatani M, Kobayashi A, Yokawa T, Maruno, Kato A, Ohnishi T, Kohmura E, Tohyama M, Yoshimine T (2000) Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat. Brain Res Mol Brain Res 78: 131–137

    Article  PubMed  CAS  Google Scholar 

  21. Taylor RG, McCall CE, Thrall RS, Woodruff RD, O’Flaherty JT (1985) Histopathologic features of phorbol myristate acetate-induced lung injury. Lab Invest 52: 61–70

    PubMed  CAS  Google Scholar 

  22. Venero JL, Vizuete ML, Ilundain AA, Machado A, Echevarria M, Cano J (1999) Detailed localization of aquaporin-4 messenger RNA in the CNS: preferential expression in periventricular organs. Neuroscience 94: 239–250

    Article  PubMed  CAS  Google Scholar 

  23. Won JS, Song DK, Kim YH, Huh SO, Suh WH (1998) The stimulation of rat astrocytes with phorbol-12-myristate-13-acetate increases the proenkephalin mRNA: involvement of proto-oncogenes. Brain Res Mol Brain Res 54: 288–297

    Article  PubMed  CAS  Google Scholar 

  24. Wright EM, Loo DD (2000) Coupling between Na+, sugar, and water transport across the intestine. Ann N Y Acad Sci 915: 54–66

    Article  PubMed  CAS  Google Scholar 

  25. Yamamoto N, Sobue K, Miyachi T, Inagaki M, Miura Y, Katsuya H, Asai K (2001) Differential regulation of aquaporin expression in astrocytes by protein kinase C. Brain Res Mol Brain Res 95: 110–116

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Neurosurgery, Virginia Commonwealth University Medical Center, 1101 East Marshall Street, Box 980508, Richmond, VA, 23298-0508, USA

    A. Marmarou

  2. Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA

    A. Kleindienst, G. Fazzina, A. M. Amorini, J. G. Dunbar, R. Glisson & A. Marmarou

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  1. A. Kleindienst
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  2. G. Fazzina
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  3. A. M. Amorini
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  4. J. G. Dunbar
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  5. R. Glisson
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  6. A. Marmarou
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Editor information

Editors and Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA

    Julian T. Hoff , Richard F. Keep , Guohua Xi  & Ya Hua , ,  & 

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© 2006 Springer-Verlag

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Kleindienst, A., Fazzina, G., Amorini, A.M., Dunbar, J.G., Glisson, R., Marmarou, A. (2006). Modulation of AQP4 expression by the protein kinase C activator, phorbol myristate acetate, decreases ischemia-induced brain edema. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_81

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  • DOI: https://doi.org/10.1007/3-211-30714-1_81

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-30712-0

  • Online ISBN: 978-3-211-30714-4

  • eBook Packages: MedicineMedicine (R0)

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