کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5861081 | 1562711 | 2016 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells](/preview/png/5861081.png)
- Mn could cause mitochondria damage and apoptosis in a dose-dependent manner in dopaminergic SH-SY5Y cells.
- Mn could induce PINK1/Parkin-mediated mitophagy.
- Mitophagy exerts significant neuro-protective effect against Mn-induced dopaminergic SH-SY5Y cells death.
Manganese (Mn) as an environmental risk factor of Parkinson's disease (PD) is considered to cause manganism. Mitophagy is thought to play a key role in elimination the injured mitochondria. The goal of this paper was to explore whether the PINK1/Parkin-mediated mitophagy is activated and its role in Mn-induced mitochondrial dysfunction and cell death in SH-SY5Y cells. Here, we investigated effects of MnCl2 on ROS generation, mitochondrial membrane potential (MMP/ÎΨm) and apoptosis by FACS and examined PINK1/Parkin-mediated mitophagy by western-blotting and the co-localization of mitochondria and acidic lysosomes. Further, we explore the role of mitophagy in Mn-induced apoptosis by inhibition the mitophagy by knockdown Parkin level. Results show that MnCl2 dose-dependently caused ÎΨm decrease, ROS generation and apoptosis of dopaminergic SH-SY5Y cells. Moreover, Mn could induce mitophagy and PINK1/Parkin-mediated pathway was activated in SH-SY5Y cells. Transient transfection of Parkin siRNA knockdown the expressing level of parkin inhibited Mn-induced mitophagy and aggravated apoptosis of SH-SY5Y cells. In conclusion, our study demonstrated that Mn may induce PINK1/Parkin-mediated mitophagy, which may exert significant neuro-protective effect against Mn-induced dopaminergic neuronal cells apoptosis.
Journal: Toxicology in Vitro - Volume 34, August 2016, Pages 212-219