Accession Number : ADA286074


Title :   Protein Kinase C is a Mediator of Lipopolysaccharide-Induced Vascular Suppression in the Rat Aorta


Descriptive Note : Journal article


Corporate Author : NAVAL MEDICAL RESEARCH INST BETHESDA MD


Personal Author(s) : McKenna, Thomas M. ; Clegg, Joanne M. ; Williams, Taffy J.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA286074


Report Date : 1994


Pagination or Media Count : 8


Abstract : Treatment of vascular tissue with lipopolysaccharide (LPS) in vitro induces hyporesponsiveness to contractile agonists. We investigated whether protein kinase C (PKC) transduces the LPS signal into contractile dysfunction. Rat aortic tissue was incubated .5-18 h with LPS (10 or 30 ng/mL) or alpha and Beta-phorbol 12,13-dibutyrate (PDB, .1 or 1 p micrometer), either alone or combined with cycloheximide (50 p micrometer) or the kinase inhibitors sphingosine (20 p micrometer), H7 (1-(5-isoquinolinylsulfonyl)-2-methyl piperazine, 25 p micrometer), and HA1004 (N-(2-guanidinoethyl)-5- isoquinolinesulfonamide, 25 p micrometer). LPS and Beta-PDB induced a sustained translocation of PKC activity from the cytosol to the membrane, an increased protein synthesis-dependent expression of nitric oxide synthase (NOS) activity, and an impaired contractility that could be partially reversed by treatment with the NOS inhibitor N-nitro-L-arginine methyl ester. Incubation with alpha-PDB, ah inactive isomer of Beta-PDB, did not alter any of the tissue functions. Sphingosine blocked LPS- and Beta-PDB-induced NOS activity and LPS-induced impairments in tissue contractility and PKC translocation. Incubation with H7 also protected against LPS-induced vasoplegia, while HA1004, used as a negative control for H7, provided little protection against LPS. These data indicate that PKC plays a role as an intracellular mediator of LPS-induced NOS activity and vascular suppression.


Descriptors :   *AORTA , *LIPOPOLYSACCHARIDES , CONTROL , FUNCTIONS , REPRINTS , RATS , SYNTHESIS , PROTEINS , IN VITRO ANALYSIS , ISOMERS , OXIDES , SIGNALS , PROTECTION , MEMBRANES , INCUBATION , INHIBITORS , SYNTHASES , NITRIC ACID , ESTERS , PHOSPHORUS TRANSFERASES , SEPTIC TANKS , MICROMETERS , TRANSLOCATION , PIPERAZINES , SUPPRESSION , DYSFUNCTION


Subject Categories : BIOCHEMISRTY
      ANATOMY AND PHYSIOLOGY


Distribution Statement : APPROVED FOR PUBLIC RELEASE