title: Evidence for phosphatidylinositol-3-OH-kinase (PI3-kinase) involvement in Cd-mediated oxidative effects on hemocytes of mussels.
abstract: This study investigated phosphatidylinositol-3-OH-kinase (PI3-kinase) involvement in the induction of cadmium-mediated oxidative effects on hemocytes of mussel Mytilus galloprovincialis. PI3-kinase was investigated with the use of wortmannin, a specific covalent inhibitor of PI3-kinase. Moreover, phorbol-myristate acetate (PMA), a well-known protein kinase C (PKC)-mediated NADPH oxidase and nitric oxide (NO) synthase stimulator, was also used for elucidating PI3-kinase involvement during the respiratory burst process in challenge hemocytes. According to the results, cells pre-treated with non-toxic concentrations of wortmannin (1 and/or 50 nM, as revealed by neutral red retention assay) for 15 min, showed a significant attenuation of cadmium ability (at concentration of 50 μM) to promote cell death, superoxide anion (O(2)(-)) production, NO generation and lipid peroxidation (in terms of malondialdehyde equivalents). On the other hand, wortmannin-treated cells showed a significant attenuation of PMA ability to induce NO generation but not O(2)(-) production. These findings reveal that PI3-kinase could lead to a PKC-independent induction of NO synthase activity in cells faced with pro-oxidants, such as cadmium, while its activation could be fundamental for the regulation of NAPDH oxidase activity, probably through a PKC-dependent signaling pathway.
authors.affiliation: Department of Biology, Section of Animal Biology, University of Patras, 26500, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Vouras
authors.forename: Stefanos
authors.initials: S
authors.lastname: Dailianis
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D006434:Hemocytes / Q000187:drug effects* / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D049878:Mytilus / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D019256:Cadmium Chloride; D008315:Malondialdehyde; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D014874:Water Pollutants, Chemical; D000077191:Wortmannin