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Compartmentalized redox signaling at the myoendothelial junction regulates heterocellular communication in the vessel wall
Author(s) -
Straub Adam,
Billaud Marie,
Johnstone Scott R.,
Best Angela K.,
LooftWilson Robin,
Gaston Ben,
Palmer Lisa,
Isakson Brant E.
Publication year - 2011
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.25.1_supplement.1093.14
Subject(s) - gap junction , s nitrosylation , nitric oxide , connexin , nitrosylation , enos , microbiology and biotechnology , nitric oxide synthase type iii , stimulation , chemistry , biology , vasodilation , s nitrosoglutathione , nitric oxide synthase , biophysics , anatomy , cysteine , biochemistry , intracellular , endocrinology , glutathione , enzyme
Regulation of vascular tone requires coordinated gap junction (GJ) communication between endothelial cells (EC) and vascular smooth muscle cells (SMC) at the myoendothelial junction (MEJ); however the post translational mechanisms that regulate GJ proteins at the MEJ remain unclear. Thus, we tested if the post‐translational redox state of connexin 43 (Cx43) regulated GJ permeability at the MEJ. Initial vasoreactivity studies on thoracodorsal arteries showed that GJs and nitric oxide (NO) blockers enhance vasoconstriction after phenylephrine (PE) application, correlating with localized endothelial nitric oxide synthase (eNOS) and Cx43 expression at the MEJ. We found an active pool of eNOS only at the MEJ, which associated with constitutive S‐nitrosylation of Cx43 on cysteine 271. Stimulation of SMCs with PE promoted Cx43 denitrosylation only at the MEJ after 1 min, followed by a renitrosylation after 20 mins. Using caged IP 3 to measure GJ permeability, we found that S‐nitrosylation of Cx43 enhanced permeability and denitrosylation decreased permeability. We identified the denitrosylase S‐nitrosoglutathione reductase (GSNO‐R) at the MEJ and found that inhibition of GSNO‐R limited Cx43 denitrosylation after PE stimulation and maintained permeable GJs. These results show that the redox state of Cx43 is critical to coordinate heterocellular communication within the vessel wall.