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| Content Provider | Springer Nature Link |
|---|---|
| Author | Sawant, Devendra A. Wilson, Rickesha L. Tharakan, Binu Stagg, Hayden W. Hunter, Felicia A. Childs, Ed W. |
| Copyright Year | 2014 |
| Abstract | Tumor necrosis factor-α (TNF-α), a pro-apoptotic cytokine, is involved in vascular hyperpermeability, tissue edema, and inflammation. We hypothesized that TNF-α induces microvascular hyperpermeability through the mitochondria-mediated intrinsic apoptotic signaling pathway. Rat lung microvascular endothelial cells grown on Transwell inserts, chamber slides, or dishes were treated with recombinant TNF-α (10 ng/ml) in the presence or absence of a caspase-3 inhibitor, Z-DEVD-FMK (100 μM). Fluorescein isothiocyanate (FITC)-albumin (5 mg/ml) was used as a marker of monolayer permeability. Mitochondrial reactive oxygen species (ROS) was determined using dihydrorhodamine 123 and mitochondrial transmembrane potential using JC-1. The adherens junction integrity and actin cytoskeletal organization were studied using β-catenin immunofluorescence and rhodamine phalloidin, respectively. Caspase-3 activity was measured fluorometrically. The pretreatment with Z-DEVD-FMK (100 μM) attenuated TNF-α-induced (10 ng/ml) disruption of the adherens junctions, actin stress fiber formation, increased caspase-3 activity, and monolayer hyperpermeability (p < 0.05). TNF-α (10 ng/ml) treatment resulted in increased mitochondrial ROS formation and decreased mitochondrial transmembrane potential. Intrinsic apoptotic signaling-mediated caspase-3 activation plays an important role in regulating TNF-α-induced endothelial cell hyperpermeability. |
| Starting Page | 971 |
| Ending Page | 980 |
| Page Count | 10 |
| File Format | |
| ISSN | 11387548 |
| Journal | Journal of Physiology and Biochemistry |
| Volume Number | 70 |
| Issue Number | 4 |
| e-ISSN | 18778755 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2014-11-14 |
| Publisher Institution | University of Navarra, Spain |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Vascular permeability Adherens junction VE-cadherin β-Catenin Mitochondria Caspase-3 Biomedicine general Human Physiology Animal Physiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Medicine Biochemistry |
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