ArticleAmerican journal of physiology. Cell physiology2014
Protein kinase G increases antioxidant function in lung microvascular endothelial cells by inhibiting the c-Abl tyrosine kinase.
Article in American journal of physiology. Cell physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
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- Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming.Nature communications · 2020Article
- The Dual Role of Microglia in Blood-Brain Barrier Dysfunction after Stroke.Current neuropharmacology · 2020Review
- Intracellular signal transduction pathways as potential drug targets for ischemia-reperfusion injury in lung transplantation.Journal of thoracic disease · 2018Article
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- Parkin regulates lipopolysaccharide-induced proinflammatory responses in acute lung injury.Translational research : the journal of laboratory and clinical medicine · 2017Article
- Lung Circulation.Comprehensive Physiology · 2016Review
- Hydrogen peroxide-induced calcium influx in lung microvascular endothelial cells involves TRPV4.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Imatinib attenuates inflammation and vascular leak in a clinically relevant two-hit model of acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- The tyrosine kinase inhibitor imatinib prevents lung injury and death after intravenous LPS in mice.Physiological reports · 2015Article
- Targeting Abl kinases to regulate vascular leak during sepsis and acute respiratory distress syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2015Review
- Differential and opposing effects of imatinib on LPS- and ventilator-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Arg mediates LPS-induced disruption of the pulmonary endothelial barrier.Vascular pharmacologyArticle
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Oxidant injury contributes to acute lung injury (ALI). We previously reported that activation of protein kinase GI (PKGI) posttranscriptionally increased the key antioxidant enzymes catalase and glutathione peroxidase 1 (Gpx-1) and attenuated oxidant-induced cytotoxicity in mouse lung microvascular endothelial cells (MLMVEC). The present studies tested the hypothesis that the antioxidant effect of PKGI is mediated via inhibition of the c-Abl tyrosine kinase. We found that activation of PKGI with the cGMP analog 8pCPT-cGMP inhibited c-Abl activity and decreased c-Abl expression in wild-type but not PKGI(-/-) MLMVEC. Treatment of wild-type MLMVEC with atrial natriuretic peptide also inhibited c-Abl activation. Moreover, treatment of MLMVEC with the c-Abl inhibitor imatinib increased catalase and GPx-1 protein in a posttranscriptional fashion. In imatinib-treated MLMVEC, there was no additional effect of 8pCPT-cGMP on catalase or GPx-1. The imatinib-induced increase in antioxidant proteins was associated with an increase in extracellular H2O2 scavenging by MLMVEC, attenuation of oxidant-induced endothelial barrier dysfunction, and prevention of oxidant-induced endothelial cell death. Finally, in the isolated perfused lung, imatinib prevented oxidant-induced endothelial toxicity. We conclude that cGMP, through activation of PKGI, inhibits c-Abl, leading to increased key antioxidant enzymes and resistance to lung endothelial oxidant injury. Inhibition of c-Abl by active PKGI may be the downstream mechanism underlying PKGI-mediated antioxidant signaling. Tyrosine kinase inhibitors may represent a novel therapeutic approach in oxidant-induced ALI.
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