| First Author | Hawkins BJ | Year | 2007 |
| Journal | Mol Cell Biol | Volume | 27 |
| Issue | 21 | Pages | 7582-93 |
| PubMed ID | 17724077 | Mgi Jnum | J:129082 |
| Mgi Id | MGI:3768617 | Doi | 10.1128/MCB.00493-07 |
| Citation | Hawkins BJ, et al. (2007) G protein-coupled receptor Ca2+-linked mitochondrial reactive oxygen species are essential for endothelial/leukocyte adherence. Mol Cell Biol 27(21):7582-93 |
| abstractText | Receptor-mediated signaling is commonly associated with multiple functions, including the production of reactive oxygen species. However, whether mitochondrion-derived superoxide (mROS) contributes directly to physiological signaling is controversial. Here we demonstrate a previously unknown mechanism in which physiologic Ca(2+)-evoked mROS production plays a pivotal role in endothelial cell (EC) activation and leukocyte firm adhesion. G protein-coupled receptor (GPCR) and tyrosine kinase-mediated inositol 1,4,5-trisphosphate-dependent mitochondrial Ca(2+) uptake resulted in NADPH oxidase-independent mROS production. However, GPCR-linked mROS production did not alter mitochondrial function or trigger cell death but rather contributed to activation of NF-kappaB and leukocyte adhesion via the EC induction of intercellular adhesion molecule 1. Dismutation of mROS by manganese superoxide dismutase overexpression and a cell-permeative superoxide dismutase mimetic ablated NF-kappaB transcriptional activity and facilitated leukocyte detachment from the endothelium under simulated circulation following GPCR- but not cytokine-induced activation. These results demonstrate that mROS is the downstream effector molecule that translates receptor-mediated Ca(2+) signals into proinflammatory signaling and leukocyte/EC firm adhesion. |
