Department of Biosciences, Biotechnology and Biofarmaceutics, University of Bari "A. Moro", 70126 Bari, Italy.
Department of Biosciences, Biotechnology and Biofarmaceutics, University of Bari "A. Moro", 70126 Bari, Italy.
Toxicology. 2022 Apr 30;472:153179. doi: 10.1016/j.tox.2022.153179. Epub 2022 Apr 13.
Toxic effects of lead (Pb) are principally manifested in the central nervous system (CNS) and a mounting body of evidence indicates that excessive chronic exposure to Pb participates in the pathological processes of numerous neurodegenerative disorders in humans.In this study we evaluated whether the prolonged pre- and postnatal exposure of rat pups to lead, administrated through ingestion in drinking water, as a typical environmental exposure, can determine alterations of the protein pattern of CNS myelin and the induction of myelin-associated proteinases. Pregnant dams were given distilled water or 0.3 mg/mL lead acetate in drinking water during gestation and lactation. At postnatal day (PND) 21, pups born from mothers poisoned with Pb continued the treatment with the metal. On PND 35 and 56, pups were sacrificed, and brains were subjected to myelin purification and extraction of myelin-associated proteinases. The SDS-PAGE analysis of protein pattern of myelin incubated in vitro with an oxidative system indicated that myelin proteins from Pb-treated pups were more sensitive to the toxicity of reactive oxygen species in comparison with those from untreated pups. The zymografic analysis of NaCl-extracts from myelin of Pb-treated pups showed a band of digestion of 54 kDa that increased in pups sacrificed at PND 56 in comparison with those sacrificed at PND 35 and correlated with the concentration of Pb, detected in purified myelin. The incubation of the NaCl-extract from Pb-treated pups with purified myelin basic protein (MBP) evidenced the presence of different MBP-degrading activities. These results suggest that Pb may influence the integrity of the myelin sheath, probably through the induction of anti-myelin proteinases.
铅（Pb）的毒性作用主要表现在中枢神经系统（CNS），越来越多的证据表明，过量的慢性 Pb 暴露参与了人类许多神经退行性疾病的病理过程。在这项研究中，我们评估了通过饮水摄入 Pb（一种典型的环境暴露）对大鼠幼仔进行长期产前和产后暴露是否会导致中枢神经系统髓鞘蛋白模式的改变，并诱导髓鞘相关蛋白酶。妊娠母鼠在妊娠期和哺乳期给予蒸馏水或 0.3mg/ml 醋酸铅饮用水。在出生后第 21 天（PND），从 Pb 中毒的母鼠中出生的幼仔继续用金属处理。在 PND 35 和 56，处死幼仔，大脑进行髓鞘纯化和髓鞘相关蛋白酶提取。体外与氧化系统孵育的髓鞘蛋白图谱 SDS-PAGE 分析表明，与未处理的幼仔相比，来自 Pb 处理幼仔的髓鞘蛋白对活性氧毒性更敏感。来自 Pb 处理幼仔的 NaCl 提取物的酶谱分析显示，54kDa 的消化带在 PND 56 处死的幼仔中比在 PND 35 处死的幼仔中增加，并且与纯化髓鞘中检测到的 Pb 浓度相关。用纯化的髓鞘碱性蛋白（MBP）孵育来自 Pb 处理幼仔的 NaCl 提取物证明存在不同的 MBP 降解活性。这些结果表明，Pb 可能通过诱导抗髓鞘蛋白酶来影响髓鞘鞘的完整性。
