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Protein kinase C beta II inhibitor attenuates leukocyte‐endothelial interactions during acute endothelial dysfunction
Author(s) -
Rueter Brian Matthew,
Chen Qian,
Young Lindon Howard
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.762.9
Subject(s) - protein kinase c , intravital microscopy , nitric oxide , superoxide , chemistry , pharmacology , nitric oxide synthase , in vivo , endocrinology , medicine , kinase , biology , biochemistry , microcirculation , enzyme , microbiology and biotechnology
Vascular dysfunction in diabetic patients and animal models is characterized by an increased inflammatory response that is mediated by increased leukocyte‐endothelial interactions. Protein kinase C (PKC) inhibition has been attributed to attenuate these interactions. However, the role of a selective PKC beta II inhibitor regulating endothelial‐leukocyte interactions has not been evaluated in vivo in real‐time. The effect of PKC beta II peptide inhibitor on leukocyte‐endothelial interactions in rat mesenteric postcapillary venule circulation was determined by using intravital microscopy. We found that superfusion of N G ‐nitro‐L‐arginine methyl ester (L‐NAME, 50 µM), a nitric oxide synthase inhibitor (n=10), significantly increased leukocyte rolling, adherence, and transmigration within a 2 hour period compared to Krebs' buffer control rats (n=7, P<0.01). However, PKC beta II inhibitor (1.0 µM, n=8/ 5.0 µM, n=7) dose‐dependently attenuated these leukocyte‐endothelial interactions compared to L‐NAME alone (P<0.05). Moreover, PKC beta II peptide inhibitor dose‐dependently decreased superoxide release from neutrophils compared to controls (P<0.01). In summary, the PKC beta II inhibitor attenuates leukocyte‐endothelial interactions that may be related to inhibiting superoxide release from neutrophils. This study was supported by Center for Chronic Disorders of Aging at PCOM.