Hypertensive encephalopathy and the blood-brain barrier: is deltaPKC a gatekeeper?

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Chou WH;Chou WH; Messing RO
  • Source:
    The Journal of clinical investigation [J Clin Invest] 2008 Jan; Vol. 118 (1), pp. 17-20.
  • Publication Type:
    Comment; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Print ISSN: 0021-9738 (Print) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
    • Publication Information:
      Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
      Original Publication: New Haven [etc.] American Society for Clinical Investigation.
    • Subject Terms:
      Blood-Brain Barrier/*enzymology ; Hypertensive Encephalopathy/*drug therapy ; Oligopeptides/*pharmacokinetics ; Oligopeptides/*therapeutic use ; Protein Kinase C-delta/*antagonists & inhibitors ; Protein Kinase Inhibitors/*pharmacokinetics ; Protein Kinase Inhibitors/*therapeutic use; Animals ; Blood-Brain Barrier/pathology ; Brain Edema/drug therapy ; Brain Edema/enzymology ; Brain Edema/pathology ; Capillary Permeability/drug effects ; Endothelium, Vascular/enzymology ; Endothelium, Vascular/pathology ; Hypertensive Encephalopathy/enzymology ; Hypertensive Encephalopathy/pathology ; Male ; Protein Kinase C-delta/metabolism ; Rats ; Rats, Inbred Dahl ; Rats, Sprague-Dawley ; Tight Junctions/enzymology ; Tight Junctions/pathology
    • Abstract:
      Hypertensive encephalopathy is a life-threatening condition due to elevation of cerebral perfusion pressure beyond the limits of autoregulation. Breakdown of the blood-brain barrier (BBB) leads to cerebral edema and reduced blood flow. In this issue of the JCI, Mochly-Rosen and colleagues demonstrate a novel molecular strategy for preserving the BBB in a model of hypertension-induced encephalopathy (see the related article beginning on page 173). Using a rationally designed peptide inhibitor of deltaPKC, they stabilized the BBB and improved mortality in hypertensive rats. This study highlights the therapeutic potential of deltaPKC inhibitors in hypertensive encephalopathy and provides incentive to elucidate deltaPKC signaling pathways that mediate BBB dysfunction in other disease states.
    • Comments:
      Comment on: J Clin Invest. 2008 Jan;118(1):173-82. doi: 10.1172/JCI32636. (PMID: 18097471)
    • References:
      Pharmacol Rev. 2005 Jun;57(2):173-85. (PMID: 15914466)
      Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11114-9. (PMID: 11553773)
      J Cereb Blood Flow Metab. 2007 Aug;27(8):1463-75. (PMID: 17293847)
      J Biol Chem. 2004 Nov 12;279(46):47985-91. (PMID: 15339931)
      J Clin Invest. 2008 Jan;118(1):173-82. (PMID: 18097471)
      Int J Biochem Cell Biol. 2004 Jul;36(7):1206-37. (PMID: 15109567)
      Science. 1995 Apr 14;268(5208):247-51. (PMID: 7716516)
      Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1485-94. (PMID: 11893586)
      Nat Rev Drug Discov. 2007 Aug;6(8):650-61. (PMID: 17667956)
      Brain Res. 2007 May 4;1144:146-55. (PMID: 17350602)
      Biochem J. 2004 Dec 15;384(Pt 3):449-59. (PMID: 15491280)
      Science. 1999 Sep 3;285(5433):1569-72. (PMID: 10477521)
      Nat Methods. 2007 Jun;4(6):511-6. (PMID: 17486086)
      Am J Hypertens. 2001 Dec;14(12):1270-2. (PMID: 11775137)
      Circulation. 2003 Nov 11;108(19):2304-7. (PMID: 14597593)
      Nat Rev Neurosci. 2006 Jan;7(1):41-53. (PMID: 16371949)
      Cardiovasc Res. 2007 Mar 1;73(4):699-709. (PMID: 17234167)
      J Neurosci. 2004 Aug 4;24(31):6880-8. (PMID: 15295022)
    • Grant Information:
      R01 AA013588 United States AA NIAAA NIH HHS; R37 AA013588 United States AA NIAAA NIH HHS; R21 NS057195 United States NS NINDS NIH HHS; NS057195 United States NS NINDS NIH HHS; AA013588 United States AA NIAAA NIH HHS
    • Accession Number:
      0 (Oligopeptides)
      0 (Protein Kinase Inhibitors)
      0 (Ser-Phe-Asn-Ser-Tyr-Glu-Leu-Gly-Glu-Ser-Leu)
      EC 2.7.1.- (Prkcd protein, rat)
      EC 2.7.11.13 (Protein Kinase C-delta)
    • Publication Date:
      Date Created: 20071222 Date Completed: 20080414 Latest Revision: 20211020
    • Publication Date:
      20250114
    • Accession Number:
      PMC2147677
    • Accession Number:
      10.1172/JCI34516
    • Accession Number:
      18097480