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PDE6s are heterogeneously distributed in native endothelium of mesenteric arteries from mice
Author(s) -
Blanchette Alexandre,
Toussaint Fanny,
Charbel Chimène,
Comtois Philippe,
Ledoux Jonathan
Publication year - 2012
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.26.1_supplement.1129.20
Subject(s) - microbiology and biotechnology , intracellular , endothelium , endothelial stem cell , phosphodiesterase , chemistry , biology , confocal microscopy , cyclic nucleotide , nucleotide , biochemistry , endocrinology , in vitro , gene , enzyme
Cyclic nucleotides (cGMP, cAMP) being key components of cellular pathways, their local levels are the core of important regulatory mechanisms. Although endothelium is the foremost vascular producer of NO, regulatory mechanisms of the NO/cGMP remain to be determined in endothelial cells. Polarity of native endothelial cells also suggests potential cyclic nucleotides microdomains. cGMP‐specific phosphodiesterases, PDE5 and PDE9, have previously been identified in endothelial cells. However, both active isoforms of retina‐restricted PDE6 (α & β) appear to be expressed in native endothelial cells as well. In opposition to PDE5 which is homogeneously distributed in endothelial cells, both PDE6s appear to be localized at the nuclear membrane interface as evidenced by confocal microscopy. However, α isoform is sparsely distributed while β forms a continuous perinuclear ring. Interestingly, PDE6s could not be detected in cultured endothelial cell lines. Dynamic mathematical modeling revealed that the experimental intracellular distributions of PDE6s and PDE5 have a significant impact on local cGMP levels, especially in the perinuclear region where cGMP levels are reduced significantly in response to a pulse of NO. Combined experimental and modeling results suggest that PDE6 might have a significant impact on cGMP‐dependent endothelial function in native arteries. Supported by FRSQ, NSERC and HSFC.