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Proteomic approaches to investigate age related vulnerability to lindane induced neurodegenerative effects in rats
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-04-01 , DOI: 10.1016/j.fct.2018.03.049
Anubha Mudawal , Ankita Srivastava , Anshuman Singh , Jai Shankar , Sanjay Yadav , Manisha Mishra , Pradhyumna K. Singh , Vinay K. Khanna , Devendra Parmar

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.



中文翻译:

蛋白质组学方法研究与年龄有关的林丹易感大鼠神经退行性作用的脆弱性

在未成熟(3周),成年(18周)和成年(48周)大鼠中进行了蛋白质组学研究,以了解年龄依赖性林丹诱发神经变性的脆弱性。从林丹处理的大鼠(2.5 mg / kg; po X 21天)中分离出的海马和黑质蛋白提取物的二维和蛋白质印迹分析表明,与泛素蛋白酶体途径,抗氧化活性,分子伴侣相关的蛋白表达显着失调,能量代谢,钙稳态和神经变性涉及的蛋白质。这些改变与林丹治疗大鼠的活性氧形成,脂质过氧化,谷胱甘肽含量降低和抗氧化酶活性显着增加有关。老年鼠 与未成熟或成年大鼠相比,这些蛋白质尤其表现出更高的变化幅度。参与细胞凋亡和自噬的蛋白质也表现出明显的表达变化,特别是在老年大鼠中。超微结构分析显示,老年大鼠海马和黑质中自噬囊泡数量增加。数据表明,蛋白质组学方法可用于研究林丹诱发大鼠神经变性的脆弱性。

更新日期:2018-04-01
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