Involvement of Na+/H+ exchanger and respiratory burst enzymes NADPH oxidase and NO synthase, in Cd-induced lipid peroxidation and DNA damage in haemocytes of mussels
Involvement of Na+/H+ exchanger and respiratory burst enzymes NADPH oxidase and NO synthase, in Cd-induced lipid peroxidation and DNA damage in haemocytes of mussels
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DOI：
10.1016/j.cbpc.2010.06.001
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发表时间：
2010-09-01
影响因子：
3.9
通讯作者：
Dailianis, Stefanos
中科院分区：
文献类型：
--
作者：
Banakou, Eleni;Dailianis, Stefanos
本研究探讨了镉诱导贻贝血细胞脂质过氧化和DNA损伤等氧化和遗传毒性效应，以及Na+/H+交换器（NHE）和呼吸爆发的主要酶NADPH氧化酶和一氧化氮（NO）合酶在镉毒性诱导中的可能作用。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，在每种情况下使用抑制剂如乙基-N-异丙基氨氯吡嗪（EIPA）、氯化二苯碘铵（DPI）和N-G-硝基-L-精氨酸甲酯（L-NAME）。此外，佛波醇肉豆蔻酸酯乙酸酯（PMA），一个众所周知的蛋白激酶C（PKC）介导的NADPH氧化酶和NO合成酶刺激剂，以及过氧化氢（H2 O2），一个众所周知的遗传毒性剂，也被用来阐明细胞内的信号分子的调制，从而导致脂质过氧化和DNA损伤的诱导。本研究的结果表明，微摩尔浓度的镉（0.05-50 μ M）可以增强脂质过氧化和DNA损伤，这可能是通过PKC介导的信号通路与NHE的参与，从而导致NADPH氧化酶和NO合酶活性的诱导，因为抑制NHE或NADPH氧化酶和NO合酶活性，在每种情况下，显著减弱Cd诱导的毒性作用。(C)2010年爱思唯尔公司All rights reserved.
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-isopropylamiloride (EIPA), diphenyleneiodonium chloride (DPI) and N-G-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 mu M) 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. (C) 2010 Elsevier Inc. All rights reserved.