Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhavan, 31, M.G. Marg, Lucknow-226 001, U.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201 002, India.
Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhavan, 31, M.G. Marg, Lucknow-226 001, U.P., India.
Food Chem Toxicol. 2018 May;115:499-510. doi: 10.1016/j.fct.2018.03.049. Epub 2018 Apr 1.
Proteomic studies were carried out in immature (3 week), adult (18 week) and aged (48 week) rats to understand the age dependent vulnerability to lindane induced neurodegeneration. 2-D and western blot analysis of protein extracts of hippocampus and substantia-nigra isolated from lindane treated rats (2.5 mg/kg; p.o. X 21 days) revealed marked dysregulation in the expression of proteins related to ubiquitin proteasome pathway, antioxidant activity, chaperones, energy metabolism, calcium homeostasis and proteins involved in neurodegeneration. These alterations were associated with marked increase in reactive oxygen species formation, lipid peroxidation, reduced glutathione content and antioxidant enzyme activities in lindane treated rats. Aged rats, in particular showed higher magnitude of alteration in these proteins when compared to immature or adult rats. Proteins involved in apoptosis and autophagy also showed marked alterations in their expression, particularly in the aged rats. Ultrastructural analysis revealed greater number of autophagic vesicle in hippocampus and substantia-nigra in treated aged rats. The data suggest that proteomic approaches could be used to investigate the vulnerability to lindane induced neurodegeneration in rats.
为了了解林丹诱导的神经退行性变在年龄依赖性方面的易感性，我们对 3 周龄（未成熟）、18 周龄（成年）和 48 周龄（老年）大鼠进行了蛋白质组学研究。对来自林丹处理大鼠（2.5mg/kg；口服，21 天）的海马体和黑质提取物的蛋白质进行 2-D 和 Western blot 分析，结果显示与泛素蛋白酶体途径、抗氧化活性、伴侣蛋白、能量代谢、钙稳态和神经退行性变相关的蛋白质表达明显失调。这些变化与林丹处理大鼠中活性氧形成、脂质过氧化、还原型谷胱甘肽含量和抗氧化酶活性的显著增加有关。与未成熟或成年大鼠相比，老年大鼠的这些蛋白质变化幅度更大。凋亡和自噬相关的蛋白质的表达也发生了明显改变，尤其是在老年大鼠中。超微结构分析显示，在处理后的老年大鼠的海马体和黑质中有更多的自噬小泡。这些数据表明，蛋白质组学方法可用于研究大鼠对林丹诱导的神经退行性变的易感性。
