کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2590859 1562083 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cadmium induced inhibition of autophagy is associated with microtubule disruption and mitochondrial dysfunction in primary rat cerebral cortical neurons
ترجمه فارسی عنوان
مهار اتفافی ناشی از کادمیوم با اختلال میکروتوبولی و اختلال عملکرد میتوکندری در نورونهای مغزی موش صحرایی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


• Cadmium induced biphasic autophagic responses and inhibition of autophagy associated with depolymerize microtubles.
• Microtuble disruption induced by Cadmium caused mitochondrial dysfunction in neurons.
• Taxol promoted mitochondria-protective autophagy via protecting microtubule from Cadmium neurotoxicity.

Recent studies have reported that mitochondria serve as direct targets for cadmium- (Cd-) induced neuronal toxicity, which can be attenuated by autophagy. The molecular mechanisms' underlying Cd-induced mitochondrial dysfunction and autophagy in neurons are not known. In this study, we studied the upstream signaling pathways induced by Cd-mediated mitochondrial metabolism alterations using primary rat neuron as a model. We found that Cd induced the destruction of microtubules (MTs), and resulted in tau hyper-phosphorylation and decreased acetylated tubulin levels, which were related to a decrease in mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels. As a result of taxol disruption, alterations in macroautophagy, like altered cellular distribution of the autophagy-related protein light chain 3 beta (LC3B) and the expression of Atg5 were found compared with Cd group. We found for the first time that MT disruption induced by Cd reduced the levels of autophagy, leading to mitochondrial dysfunction. These observations suggest new therapeutic strategies aimed to activate or ameliorate pro-survival macroautophagy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurotoxicology and Teratology - Volume 53, January–February 2016, Pages 11–18
نویسندگان
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