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Connexin40 is required for NADPH oxidase‐derived oxidant production in microvascular endothelial cells
Author(s) -
Tyml Karel,
Yu Guo,
Bolon Michael,
Shao Qing,
Laird Dale
Publication year - 2008
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.22.1_supplement.1144.1
Subject(s) - nadph oxidase , reactive oxygen species , microbiology and biotechnology , gap junction , chemistry , intracellular , connexin , biology
The function of connexins (Cx) may extend beyond gap junctional intercellular communication (GJIC). We hypothesized that Cx40 is required for NADPH oxidase‐dependent ROS production in microvascular endothelial cells subjected to hypoxia/reoxygenation (H/R), independent of GJIC. ROS generation and NADPH oxidase activation was assessed after H/R in confluent monolayers of cells of wild‐type (WT), Cx40−/−, gp91phox−/−, or p47phox−/− mice, as well as in monolayers of GJIC‐deficient SKHep1 cells overexpressing GFP‐tagged Cx40. In WT cells, H/R‐initiated ROS increase was not affected by the GJ blocker 18alpha‐glycyrrhetinic acid, nor by preventing cells from establishing contact with each other, but it was absent in Cx40−/− cells. H/R increased ROS in SKHep1 cells expressing Cx40‐GFP, but not in cells expressing the control vector. We also asked if Cx40‐dependent reduction in inter‐endothelial electrical coupling after H/R requires NADPH oxidase. H/R reduced coupling in WT and gp91phox−/− but not in p47phox−/− cells. We suggest that (1) H/R‐initiated signaling in microvascular endothelial cells involves cross‐talk between NADPH oxidase and Cx40, and (2) Cx40 is required for NADPH oxidase‐derived ROS production, independent of GJIC. (Support: HSFO).