Abstract:
Exposure of mitochondrial parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) to PC-12 cells results in significant cell death, decreases lysosomal acidity, and inhibits autophagic flux. Biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of ≈100 nm diameter localize to the lysosome, degrade, and subsequently release their acidic components to acidify the local lysosomal environment. The performance of PLGA NPs with different lysosomal pH modulating capabilities is investigated in PC-12 cells under MPP+ induced mitochondrial toxicity. PLGA NPs perform in a compositional dependent manner, where NPs with a higher glycolic acid to lactic acid ratio content degrade faster, and yield greater degrees of lysosomal pH modulation as well as autophagic flux modulation in PC-12 cells under MPP+ insult. These results show that slight compositional changes of the polymeric NP give rise to differing degrees of lysosomal acidification in PC-12 cells and afford improved cellular degradative activity.
摘要:
线粒体帕金森病神经毒素1-甲基-4-苯基吡啶鎓离子(MPP)暴露于PC-12细胞会导致明显的细胞死亡,降低溶酶体酸度,并抑制自噬通量。直径约100nm的可生物降解的聚(乳酸-羟基乙酸共聚物)(PLGA)纳米颗粒(NPs)定位于溶酶体,降解,并随后释放其酸性成分以酸化局部溶酶体环境。在MPP诱导的线粒体毒性下,在PC-12细胞中研究了具有不同溶酶体pH调节能力的PLGANP的性能。PLGANP以成分依赖的方式执行,其中具有较高乙醇酸与乳酸比例含量的NP降解更快,并在MPP损伤下PC-12细胞中产生更大程度的溶酶体pH调节以及自噬通量调节。这些结果表明,聚合物NP的轻微组成变化在PC-12细胞中引起不同程度的溶酶体酸化,并提供改善的细胞降解活性。