Effect of t-butylhydroperoxide on chloride secretion in rat tracheal epithelia.
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 microM bumetanide. N(-Diphenyl-1,4-phenylene-diamine (DPPD, 5 microM), 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-induce Isc increase was abolished. Pretreatment of indomethacin (10 microM) completely inhibited the t-butylhydroperoxide response, but pretreatment of thapsigargin (1 microM) 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 metabolities by Ca(2+)-dependent and -independent mechanisms.
Jung
J S
JS
Department of Physiology, College of Medicine, Pusan National University, Korea.
Lee
J Y
JY
Oh
S O
SO
Jang
P G
PG
Bae
H R
HR
Kim
Y K
YK
Lee
S H
SH
D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D017136:Ion Transport; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D010545:Peroxides / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism*; D020122:tert-Butylhydroperoxide
D002712:Chlorides; D016877:Oxidants; D010545:Peroxides; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide