Section of Animal Biology, Department of Biology, Faculty of Sciences, University of Patras, 26 500 Patra, Greece.
Comp Biochem Physiol C Toxicol Pharmacol. 2010 Sep;152(3):346-52. doi: 10.1016/j.cbpc.2010.06.001. Epub 2010 Jun 10.
This study investigated cadmium-induced oxidative and genotoxic effects, such as lipid peroxidation and disturbance of DNA integrity (DNA damage) in haemocytes of mussel Mytilus galloprovincialis and the possible involvement of Na+/H+ exchanger (NHE), and/or the main enzymes of respiratory burst, NADPH oxidase and nitric oxide (NO) synthase, in the induction of Cd toxic effects. In order to verify the role of either NHE, or NADPH oxidase and NO synthase in Cd-mediated toxicity, inhibitors such as ethyl-N-isopropyl-amiloride (EIPA), diphenyleneiodonium chloride (DPI) and NG-nitro-L-arginine methyl ester (L-NAME) were used in each case. Moreover, phorbol-myristate acetate (PMA), a well-known protein kinase C (PKC)-mediated NADPH oxidase and NO synthase stimulator, as well as hydrogen peroxide (H2O2), a well-known genotoxic agent, was also used for elucidating the modulation of signaling molecules within cells, thus leading to the induction of lipid peroxidation and DNA damage. The results of the present study showed that micromolar concentrations of Cd (0.05-50 microM) could enhance both lipid peroxidation and DNA damage, possible via a PKC-mediated signaling pathway with the involvement of NHE, thus leading to the induction of NADPH oxidase and NO synthase activity, since inhibition of either NHE, or NADPH oxidase and NO synthase activity, significantly attenuates Cd-induced toxic effects in each case.
本研究调查了镉诱导的氧化和遗传毒性效应,如贻贝血细胞中的脂质过氧化和 DNA 完整性(DNA 损伤)的紊乱,以及钠离子/氢离子交换器(NHE)和/或呼吸爆发的主要酶,即 NADPH 氧化酶和一氧化氮(NO)合酶,在诱导 Cd 毒性效应中的可能参与。为了验证 NHE 或 NADPH 氧化酶和 NO 合酶在 Cd 介导的毒性中的作用,在每种情况下都使用了抑制剂,如乙基-N-异丙基-amiloride(EIPA)、二苯基碘(DPI)和 NG-硝基-L-精氨酸甲酯(L-NAME)。此外,佛波醇 12,13-二丁酸酯(PMA),一种众所周知的蛋白激酶 C(PKC)介导的 NADPH 氧化酶和 NO 合酶刺激物,以及过氧化氢(H2O2),一种众所周知的遗传毒性物质,也被用于阐明细胞内信号分子的调节,从而导致脂质过氧化和 DNA 损伤的诱导。本研究的结果表明,微摩尔浓度的 Cd(0.05-50 μM)可以增强脂质过氧化和 DNA 损伤,可能通过 PKC 介导的信号通路,涉及 NHE,从而诱导 NADPH 氧化酶和 NO 合酶活性,因为抑制 NHE 或 NADPH 氧化酶和 NO 合酶活性,在每种情况下都显著减轻 Cd 诱导的毒性效应。