ET-1 mediates the release of reactive oxygen species and TNF-α in lung tissue by protein kinase C α and β1

Background the aim of this study was to determine the involvement of protein kinase c (pkc) in the et-1 induced generation of reactive oxygen species and tnf-α in rat lungs. methods experiments were performed on 6 groups of rats: group i: saline-treated control; group ii: saline followed by endothelin-1 (et-1) (3 μg/kg); group iii: saline followed by selective pkc αβ1 inhibitor (gö6976) (2 μg/kg); group iv: gö6976 (2 μg/kg) administered 30 min before et-1 (3 μg/kg); group v: saline followed by the pkc activator phorbol 12-myristate 13-acetate (pma) (50 μg/kg); group vi: gö6976 (2 μg/kg) administered 30 min before pma (50 μg/kg). after 5 h,the animals were euthanized and their lungs were isolated for measurements. results et-1 resulted in increase in thiobarbituric acid reactive substances (tbars) and hydrogen peroxide (h2o2) levels and lung edema,as well as a decrease in gsh/gssg ratio compared to the controls. the level of tnf-α also was elevated in the presence of et-1. administration of gö6976 30 min before et-1 injection significantly decreased lung edema,as well as the concentrations of tbars,h2o2 and tnf-α,but increased the gsh/gssg redox ratio compared to et-1. conversely,pma elevated lung edema and tbars,h2o2 and tnf-α concentrations,but decreased the gsh/gssg redox ratio compared to the control group. treatment with gö6976 significantly ameliorated the pma-induced oxidative stress parameters,decreased tissue tnf-α level,and lung edema. conclusion endothelin-1 induces ros generation,increases tnf-α level and lung edema via activation of pkc αβ1. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.