Cadmium effects on ROS production and DNA damage via adrenergic receptors stimulation: Role of Na+/H+ exchanger and PKC

• Published in: Free radical research 2005-10, Vol.39 (10), p.1059-1070
• Main Authors: Dailianis, Stefanos, Piperakis, Styllianos M., Kaloyianni, Martha
• Format: Article
• Language: English
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; Animals; Bivalvia - drug effects; Bivalvia - metabolism; Cadmium; Cadmium - pharmacology; cAMP; Cells, Cultured; Comet Assay; Cyclic AMP - metabolism; Digestive System - drug effects; Digestive System - metabolism; DNA - metabolism; DNA damage; DNA Damage - drug effects; Mytilus galloprovincialis; NHE; PKC; Protein Kinase C - metabolism; Reactive Oxygen Species - metabolism; Receptors, Adrenergic - metabolism; Sodium-Hydrogen Exchangers - metabolism
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715760500243765

The objective of the present study was to elucidate the events that are involved in reactive oxygen species (ROS) production and DNA damage after adrenergic receptors stimulation by cadmium, in relation to cAMP, protein kinase C (PKC) and Na+/H+ exchanger (NHE). Cadmium (50 μM) caused increased levels of ROS with a concomitant increase in DNA damage in digestive gland of Mytilus galloprovincialis. Either the use of EIPA, a NHE blocker, or calphostin C, the inhibitor of PKC, reduced cadmium effects. Cells treated with α1-, α2-, β- and β1- adrenergic antagonists together with cadmium reversed cadmium alone effects, while the respective adrenergic agonists, phenylephrine and isoprenaline, mimic cadmium effects. Moreover, cadmium caused an increase in the levels of cAMP in digestive gland cells that were reversed after NHE and PKC inhibition as well as in the presence of each type of adrenergic antagonist. The different sensitivity of α1-, α2-, β-, β1- adrenergic receptors on ROS, cAMP production and DNA damage possibly leads to the induction of two signaling pathways that may be interacting or to the presence of a compensatory pathway that acts in concert with the α- and β- adrenergic receptors. In these signaling pathways PKC and NHE play significant role.