Sandhir R, Gill K D
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Exp Mol Pathol. 1994 Aug;61(1):69-75. doi: 10.1006/exmp.1994.1026.
In the present investigation, we observed that lead in vitro activates calmodulin at lower concentrations, and the maximum activation was observed at 30 microM concentration. In vivo lead exposure (50 mg/kg body weight, intragastrically) for a period of 8 weeks also stimulated the activity of calmodulin by 45%. The addition of trifluoperazine resulted in partially inhibiting the lead-stimulated calmodulin activity, whereas the calcium-stimulated calmodulin activity was completely inhibited by trifluoperazine. Studies with purified calmodulin from the brain of control and lead-treated animals indicate that approximately 4 mole of calcium was present bound/mole of calmodulin in control animals and this fraction was reduced in lead-treated animals to approximately 3 mole of calcium/mole of calmodulin. Lead distribution revealed that approximately 68% of the total lead present was bound to calmodulin and the remaining 32% present was bound to non-calmodulin binding sites following lead exposure. These results indicate that in vivo lead exposure is able to displace and mimic the action of calcium and this may constitute a molecular mechanism of lead neurotoxicity.
在本研究中，我们观察到铅在体外较低浓度时就能激活钙调蛋白，在30微摩尔浓度时观察到最大激活作用。体内铅暴露（50毫克/千克体重，经胃给药）8周也使钙调蛋白的活性提高了45%。添加三氟拉嗪会部分抑制铅刺激的钙调蛋白活性，而钙刺激的钙调蛋白活性则被三氟拉嗪完全抑制。对对照动物和铅处理动物大脑中纯化的钙调蛋白进行的研究表明，对照动物中每摩尔钙调蛋白约有4摩尔钙与之结合，而在铅处理动物中，这一比例降至约每摩尔钙调蛋白3摩尔钙。铅分布显示，铅暴露后，总铅中约68%与钙调蛋白结合，其余32%与非钙调蛋白结合位点结合。这些结果表明，体内铅暴露能够取代并模拟钙的作用，这可能构成铅神经毒性的分子机制。
