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Possible involvement of cytoskeletal reorganization in PKC‐induced cerebroarterial constriction
Author(s) -
ELYazbi Ahmed Fawzy
Publication year - 2010
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.24.1_supplement.957.7
Subject(s) - protein kinase c , phosphorylation , calponin , caldesmon , cytoskeleton , actin , microbiology and biotechnology , chemistry , constriction , calcium , biophysics , medicine , calmodulin , endocrinology , biology , biochemistry , cell , organic chemistry
Several hypotheses have been proposed to account for force production evoked by PKC activation in the resistance circulation based on pharmacological experiments with intact and permeabilized vessel preparations. These include: an increase in calcium influx, an increase in calcium sensitization via phosphorylation of CPI‐17, and thin filament regulation via phosphorylation of calponin and/or caldesmon. However, biochemical evidence of a role for these phosphoproteins has not been forthcoming. Here, rat middle cerebral arteries were used to investigate the molecular mechanism responsible for PKC‐mediated constriction evoked by 5‐HT or direct activation with phorbol dibutyrate (PDBu). A highly sensitive 3‐step western blotting method was used to detect changes in protein phosphorylation. PDBu caused a much larger contraction compared to that evoked by a maximal concentration of 5‐HT, but a similar increase in LC20 phosphorylation. PKC inhibition with GF109302X abolished the 5‐HT‐induced constriction with minimal change in pLC20 content, indicating a role for a non‐LC20‐dependent mechanism(s). Phosphorylation of calponin and caldesmon were not affected by direct PKC activation. These findings suggest a possible contribution of actin cytoskeletal rearrangement to force generation evoked by PKC activation in resistance arteries. (CIHR MOP‐97988, CIHR & AHFMR Fellowships)