Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kolluru, GK; Tamilarasan, KP; Rajkumar, AS; Geetha Priya, S; Rajaram, M; Saleem, NK; Majumder, S; Jaffar Ali, BM; Illavazagan, G; Chatterjee, S.
Nitric oxide/cGMP protects endothelial cells from hypoxia-mediated leakiness.
Eur J Cell Biol. 2008; 87(3):147-161
Doi: 10.1016/j.ejcb.2007.10.001
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Kuppusamy Palaniappan Tamilarasan
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- Abstract:
- Leakiness of the endothelial bed is attributed to the over-perfusion of the pulmonary bed, which leads to high altitude pulmonary edema (HAPE). Inhalation of nitric oxide has been successfully employed to treat HAPE patients. We hypothesize that nitric oxide intervenes in the permeability of the pulmonary macrovascular endothelial bed to rectify the leaky bed under hypoxia. Our present work explores the underlying mechanism of 'hypoxia-mediated' endothelial malfunction by using human umbilical cord-derived immortalized endothelial cells, ECV-304, and bovine pulmonary artery primary endothelial cells. The leakiness of the endothelial monolayer was increased by two-fold under hypoxia in comparison to cells under normoxia, while optical tweezers-based tethering assays reported a higher membrane tension of endothelial cells under hypoxia. Phalloidin staining demonstrated depolymerization of F-actin stress fibers and highly polarized F-actin patterns in endothelial cells under hypoxia. Nitric oxide, 8-Br-cGMP and sildenafil citrate (phosphodiesterase type 5 inhibitor) led to recovery from hypoxia-induced leakiness of the endothelial monolayers. Results of the present study also suggest that 'hypoxia-induced' cytoskeletal rearrangements and membrane leakiness are associated with the low nitric oxide availability under hypoxia. We conclude that nitric oxide-based recovery of hypoxia-induced leakiness of endothelial cells is a cyclic guanosine monophosphate (cGMP)-dependent phenomenon.
- Find related publications in this database (using NLM MeSH Indexing)
- Actins - metabolism
- Animals -
- Capillary Permeability - physiology
- Cattle -
- Cell Hypoxia -
- Cell Line -
- Cells, Cultured -
- Cyclic GMP - metabolism
- Endothelial Cells - cytology
- Endothelium, Vascular - cytology
- Humans -
- Nitric Oxide - metabolism
- Find related publications in this database (Keywords)
- hypoxia
- endothelial cells
- nitric oxide
- actin filaments
- cGMP
- sildenafil