Sustained pharmacological inhibition of δPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats

Journal of Clinical Investigation

Volumn 118, Issue 1, 2008, Pages 173-182

  Qi, Xin ^a   Inagaki, Koichi ^a,b   Sobel, Raymond A ^a   Mochly Rosen, Daria ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b OTSU RED CROSS HOSPITAL   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

PEPTIDE DELTAV1 1; PROTEIN KINASE C DELTA; PROTEIN KINASE C INHIBITOR; TRANSACTIVATOR PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BLOOD BRAIN BARRIER; BLOOD VESSEL PERMEABILITY; CAPILLARY ENDOTHELIUM; CONTROLLED STUDY; DRUG MECHANISM; ENDOTHELIUM CELL; HYPERTENSION ENCEPHALOPATHY; MORTALITY; NEUROPROTECTION; NONHUMAN; OSMOTIC MINIPUMP; PRIORITY JOURNAL; PROTEIN FUNCTION; RAT; REGULATORY MECHANISM;

ANIMALS; BLOOD-BRAIN BARRIER; BRAIN EDEMA; CAPILLARY PERMEABILITY; ENDOTHELIUM, VASCULAR; HYPERTENSIVE ENCEPHALOPATHY; MALE; OLIGOPEPTIDES; PROTEIN KINASE C-DELTA; PROTEIN KINASE INHIBITORS; RATS; RATS, INBRED DAHL; RATS, SPRAGUE-DAWLEY; TIGHT JUNCTIONS;

EID: 38149091885     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI32636     Document Type: Article

References (57)

1. Strandgaard, S., and Paulson, O.B. 1995. Cerebrovascular damage in hypertension. J. Cardiovasc. Risk. 2:34-39.
2. Phillips, S.J., and Whisnant, J.P. 1992. Hypertension and the brain. The National High Blood Pressure Education Program. Arch. Intern. Med. 152:938-945.
3. Baumbach, G.L., and Heistad, D.D. 1988. Cerebral circulation in chronic arterial hypertension. Hypertension. 12:89-95.
4. Conen, D., Bertel, O., and Dubach, U.C. 1987. Cerebral blood flow and calcium antagonists in hypertension. J. Hypertens. Suppl. 5:S75-S80.
5. Abbott, N.J., Ronnback, L., and Hansson, E. 2006. Astrocyte-endothelial interactions at the bloodbrain barrier. Nat. Rev. Neurosci. 7:41-53.
6. Hawkins, B.T., and Davis, T.P. 2005. The bloodbrain barrier/neurovascular unit in health and disease. Pharmacol. Rev. 57:173-185.
7. Ballabh, P., Braun, A., and Nedergaard, M. 2004. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol. Dis. 16:1-13.
8. Harhaj, N.S., and Antonetti, D.A. 2004. Regulation of tight junctions and loss of barrier function in pathophysiology. Int. J. Biochem. Cell. Biol. 36:1206-1237.
9. Huber, J.D., Egleton, R.D., and Davis, T.P. 2001. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci. 24:719-725.
10. Wolburg, H., and Lippoldt, A. 2002. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul. Pharmacol. 38:323-337.
11. Davies, D.C. 2002. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J. Anat. 200:639-646.
12. Kalaria, R.N. 1992. The blood-brain barrier and cerebral microcirculation in Alzheimer disease. Cerebrovasc. Brain Metab. Rev. 4:226-260.
13. Nico, B., Roncali, L., Mangieri, D., and Ribatti, D. 2005. Blood-brain barrier alterations in MDX mouse, an animal model of the Duchenne muscular dystrophy. Curr. Neurovasc. Res. 2:47-54.
14. Prat, A., and Antel, J. 2005. Pathogenesis of multiple sclerosis. Curr. Opin. Neurol. 18:225-230.
15. Gasche, Y., and Copin, J.C. 2003. Blood-brain barrier pathophysiology and ischaemic brain oedema [In French]. Ann. Fr. Anesth. Reanim. 22:312-319.
16. Tanaka, C., and Nishizuka, Y. 1994. The protein kinase C family for neuronal signaling. Annu. Rev. Neurosci. 17:551-567.
17. Wolf, B.A., Easom, R.A., McDaniel, M.L., and Turk, J. 1990. Diacylglycerol synthesis de novo from glucose by pancreatic islets isolated from rats and humans. J. Clin. Invest. 85:482-490.
18. 2. Am. J. Physiol. 256:H1012-H1022.
19. Ramirez, M.M., Kim, D.D., and Duran, W.N. 1996. Protein kinase C modulates microvascular permeability through nitric oxide synthase. Am. J. Physiol. 271:H1702-H1705.
20. Schaffler, A., Arndt, H., Scholmerich, J., and Palitzsch, K.D. 2000. Amelioration of hyperglycemic and hyperosmotic induced vascular dysfunction by in vivo inhibition of protein kinase C and p38 MAP kinase pathway in the rat mesenteric microcirculation. Eur. J. Clin. Invest. 30:586-593.
21. Meier, M., and King, G.L. 2000. Protein kinase C activation and its pharmacological inhibition in vascular disease. Vasc. Med. 5:173-185.
22. Hempel, A., et al 1999. Calcium antagonists ameliorate ischemia-induced endothelial cell permeability by inhibiting protein kinase C. Circulation. 99:2523-2529.
23. Aiello, L.P., et al. 1997. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes. 46:1473-1480.
24. Bright, R., et al. 2004. Protein kinase C delta mediates cerebral reperfusion injury in vivo. J. Neurosci. 24:6880-6888.
25. Chou, W.H., et al. 2004. Neutrophil protein kinase C delta as a mediator of stroke-reperfusion injury. J. Clin. Invest. 114:49-56.
26. Knudsen, K.D., et al. 1970. Effects of chronic excess salt ingestion. Inheritance of hypertension in the rat. J. Exp. Med. 132:976-1000.
27. Smeda, J.S., and Payne, G.W. 2003. Alterations in autoregulatory and myogenic function in the cerebrovasculature of Dahl salt-sensitive rats. Stroke. 34:1484-1490.
28. von Lutterotti, N., et al. 1992. Angiotensin II receptor antagonist delays renal damage and stroke in salt-loaded Dahl salt-sensitive rats. J. Hypertens. 10:949-957.
29. Chen, L., et al. 2001. Opposing cardioprotective actions and parallel hypertrophic effects of delta PKC and epsilon PKC. Proc. Natl. Acad. Sci. U. S. A. 98:11114-11119.
30. Inagaki, K., et al. 2002. Tissue angiotensin II during progression or ventricular hypertrophy to heart failure in hypertensive rats; differential effects on PKC epsilon and PKC beta. J. Mol. Cell. Cardiol. 34:1377-1385.
31. +, phospholipid-dependent protein kinase associated with plasma membrane. Nature. 301:621-623.
32. Spatz, M., and Klatzo, I. 1976. Pathological aspects of brain transport phenomena. Adv. Exp. Med. Biol. 69:479-495.
33. Rubin, L.L., and Staddon, J.M. 1999. The cell biology of the blood-brain barrier. Annu. Rev. Neurosci. 22:11-28.
34. Nicchia, G.P., et al. 2004. The role of aquaporin-4 in the blood-brain barrier development and integrity: studies in animal and cell culture models. Neuroscience. 129:935-945.
35. Nico, B., et al. 2003. Severe alterations of endothelial and glial cells in the blood-brain barrier of dystrophic mdx mice. Glia. 42:235-251.
36. Chen, M.L., Pothoulakis, C., and LaMont, J.T. 2002. Protein kinase C signaling regulates ZO-1 translocation and increased paracellular flux of T84 colonocytes exposed to Clostridium difficile toxin A. J. Biol. Chem. 277:4247-4254.
37. Willott, E., et al. 1993. The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc. Natl. Acad. Sci. U. S. A. 90:7834-7838.
38. Antonetti, D.A., et al. 1999. Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechanism for vascular permeability in diabetic retinopathy and tumors. J. Biol. Chem. 274:23463-23467.
39. Fischer, S., Wobben, M., Marti, H.H., Renz, D., and Schaper, W. 2002. Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1. Microvasc. Res. 63:70-80.
40. Ohtake, K., et al. 2003. Poly-L-arginine enhances paracellular permeability via serine/threonine phosphorylation of ZO-1 and tyrosine dephosphorylation of occludin in rabbit nasal epithelium. Pharm. Res. 20:1838-1845.
41. Zhang, J.J., Chao, L., and Chao, J. 1999. Adenovirus-mediated kallikrein gene delivery reduces aortic thickening and stroke-induced death rate in Dahl salt-sensitive rats. Stroke. 30:1925-1931; discussion 1931-1932.
42. Roe, M. 2007. Targeted inhibition of delta-protein kinase C to ameliorate reperfusion injury during primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: results from the DELTA MI trial. In American College of Cardiology 56th Annual Scientific Session, i2 Summit 2007 (Innovation in Intervention) Late-Breaking Clinical Trials II, Session 2405. March 24-27. New Orleans, Louisiana, USA.
43. Murriel, C.L., Churchill, E.N., Inagaki, K., Szweda, L.I., and Mochly-Rosen, D. 2004. Protein kinase Cdelta activation induces apoptosis in response to cardiac ischemia and reperfusion damage: a mechanism involving BAD and the mitochondria. J. Biol. Chem. 279:47985-47991.
44. Inagaki, K., et al. 2003. Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo. Circulation. 108:2304-2307.
45. Churchill, E.N., Murriel, C.L., Chen, C.H., Mochly-Rosen, D., and Szweda, L.I. 2005. Reperfusion-induced translocation of deltaPKC to cardiac mitochondria prevents pyruvate dehydrogenase reactivation. Circ. Res. 97:78-85.
46. Bright, R., Steinberg, G.K., and Mochly-Rosen, D. 2007. DeltaPKC mediates microcerebrovascular dysfunction in acute ischemia and in chronic hypertensive stress in vivo. Brain Res. 1144:146-155.
47. Fleegal, M.A., Hom, S., Borg, L.K., and Davis, T.P. 2005. Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation. Am. J. Physiol. Heart Circ. Physiol. 289:H2012-H2019.
48. Nagpala, P.G., Malik, A.B., Vuong, P.T., and Lum, H. 1996. Protein kinase C beta 1 overexpression augments phorbol ester-induced increase in endothelial permeability. J. Cell. Physiol. 166:249-255.
49. Clarke, H., et al. 2000. The transient increase of tight junction permeability induced by bryostatin 1 correlates with rapid downregulation of protein kinase C-alpha. Exp. Cell Res. 261:239-249.
50. Mullin, J.M., et al. 1998. Overexpression of protein kinase C-delta increases tight junction permeability in LLC-PK1 epithelia. Am. J. Physiol. 275:C544-C554.
51. Banan, A., et al. 2002. Activation of delta-isoform of protein kinase C is required for oxidant-induced disruption of both the microtubule cytoskeleton and permeability barrier of intestinal epithelia. J. Pharmacol. Exp. Ther. 303:17-28.
52. Tinsley, J.H., Teasdale, N.R., and Yuan, S.Y. 2004. Involvement of PKCdelta and PKD in pulmonary microvascular endothelial cell hyperpermeability. Am. J. Physiol. Cell Physiol. 286:C105-C111.
53. Clarke, H., Marano, C.W., Peralta Soler, A., and Mullin, J.M. 2000. Modification of tight junction function by protein kinase C isoforms. Adv. Drug Deliv. Rev. 41:283-301.
54. Han, Z., Wax, M.B., and Patil, R.V. 1998. Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation. J. Biol. Chem. 273:6001-6004.
55. Zelenina, M., Zelenin, S., Bondar, A.A., Brismar, H., and Aperia, A. 2002. Water permeability of aquaporin-4 is decreased by protein kinase C and dopamine. Am. J. Physiol. Renal Physiol. 283:F309-F318.
56. Aschner, M. 1998. Immune and inflammatory responses in the CNS: modulation by astrocytes. Toxicol. Lett. 102-103:283-287.
57. Abbott, N.J. 2002. Astrocyte-endothelial interactions and blood-brain barrier permeability. J. Anat. 200:629-638.