| Autor: |
Jung, Jin Sup, Lee, Jin Youn, Oh, Sae Ock, Jang, Phil Gum, Bae, Hae Rahn, Kim, Yong Keun, Lee, Sang Ho |
| Zdroj: |
Pharmacology & Toxicology; 1998, Vol. 82 Issue 5, p236-242, 7p |
| Abstrakt: |
Oxidative stress has been known to play important roles in various inflammatory diseases of lung such as allergic bronchitis, dust particle-induced inflammatory diseases, or chronic bronchitis. However, the effects of oxidants on Cl secretion in tracheal epithelia have not been determined. To examine the effects of oxidants on Cl- secretion of the airway epithelia rat tracheal epithelial cells were cultured on porous filters and short circuit current (Isc) was measured in an Ussing chamber system. t-Butylhydroperoxide, which was widely used as a model substance to study the mechanism of cell injury resulted from oxidative stress, induced a transient increase in Isc by dose-dependent manner. The response was not observed in Cl- -free medium, and inhibited by 100 μM bumetanide. N(-Diphenyl-l,4-phenylene-diamine (DPPD, 5 μM), an inhibitor of lipid peroxidation, blocked the t-butylhydroperoxide response. When t-butylhydroperoxide was added after the administration of forskolin or H-89, a protein kinase A inhibitor, the t-butylhydroperoxide-induee Isc increase was abolished. Pretreatment of indomethacin (10 μM) completely inhibited the t-butylhydroperoxide response, but pretreatment of thapsigargin (1 μM) did not. t-Butylhydroperoxide induced gradual increases in cytosolic Ca2+ level, and increased [3H]arachidonic acid release in the presence of thapsigargin. These results indicate that t-butylhydroperoxide stimulates Cl- secretion via activation of phospholipase A2 and subsequent production of cyclooxygenase metabolites by Ca2+-dependent and -independent mechanisms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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