Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
Neurochem Int. 2011 Jun;58(7):776-84. doi: 10.1016/j.neuint.2011.03.002. Epub 2011 Mar 17.
The molecular events leading to neuronal dysfunction often associated with mercury toxicity can be complex and is yet to be fully elucidated. Hence, the present study sought to evaluate the interaction of inorganic mercury (Hg(2+)) with the ouabain-sensitive electrogenic pump in partially purified mammalian brain membrane preparations. The results show that Hg(2+) significantly inhibited the transmembrane enzyme in a concentration dependent manner. In addition, Hg(2+) exerts its inhibitory effect on the activity of the enzyme by interacting with groups at the adenosine triphosphate (ATP), Na(+) and K(+) binding sites. However, preincubation of the enzyme with exogenous monothiols, cysteine, prevented the inhibition of Hg(2+) on the pump's activity suggesting that Hg(2+) may be interacting with the thiols at the nucleotide (ATP) and cationic (Na(+) and K(+)) binding sites. In fact, our data show that Hg(2+) oxidizes sulphydryl groups in cysteine in a time dependent fashion in vitro. Finally, we speculate that the small molecular volume of Hg(2+) in comparison with the substrates (ATP, Na(+) and K(+)) of sodium pump, its possibly high reactivity and strong affinity for thiols may account for its high toxicity towards the membrane bound ouabain-sensitive electrogenic pump.
导致神经元功能障碍的分子事件通常与汞毒性有关，其过程可能很复杂，目前尚未完全阐明。因此，本研究试图评估无机汞 (Hg2+) 与部分纯化的哺乳动物脑膜制剂中乌本苷敏感的生电性泵之间的相互作用。结果表明，Hg2+ 以浓度依赖的方式显著抑制跨膜酶。此外，Hg2+ 通过与三磷酸腺苷 (ATP)、Na+ 和 K+ 结合位点的基团相互作用，对酶的活性发挥抑制作用。然而，将酶与外源性单硫醇、半胱氨酸预先孵育，可防止 Hg2+ 对泵活性的抑制，这表明 Hg2+ 可能与核苷酸 (ATP) 和阳离子 (Na+ 和 K+) 结合位点的巯基相互作用。事实上，我们的数据表明，Hg2+ 在体外以时间依赖的方式氧化半胱氨酸中的巯基。最后，我们推测与钠泵的底物 (ATP、Na+ 和 K+) 相比，Hg2+ 的小分子体积、其可能的高反应性和对巯基的强亲和力可能是其对膜结合乌本苷敏感的生电性泵具有高毒性的原因。
