Simultaneous activation of mitophagy and autophagy by staurosporine protects against dopaminergic neuronal cell death.

Neurosci Lett

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans university, Seoul, South Korea; Department of Brain and Cognitive Sciences, Brain Disease Research Institute, Ewha W. University, Seoul, South Korea. Electronic address:

Published: February 2014

Abnormal autophagy is frequently observed during dopaminergic neurodegeneration in Parkinson's disease (PD). However, it is not yet firmly established whether active autophagy is beneficial or pathogenic with respect to dopaminergic cell loss. Staurosporine, a common inducer of apoptosis, is often used in mechanistic studies of dopaminergic cell death. Here we report that staurosporine activates both autophagy and mitophagy simultaneously during dopaminergic neuronal cell death, and evaluate the physiological significance of these processes during cell death. First, staurosporine treatment resulted in induction of autophagy in more than 75% of apoptotic cells. Pharmacological inhibition of autophagy by bafilomycin A1 decreased significantly cell viability. In addition, staurosporine treatment resulted in activation of the PINK1-Parkin mitophagy pathway, of which deficit underlies some familial cases of PD, in the dopaminergic neuronal cell line, SN4741. The genetic blockade of this pathway by PINK1 null mutation also dramatically increased staurosporine-induced cell death. Taken together, our data suggest that staurosporine induces both mitophagy and autophagy, and that these pathways exert a significant neuroprotective effect, rather than a contribution to autophagic cell death. This model system may therefore be useful for elucidating the mechanisms underlying crosstalk between autophagy, mitophagy, and cell death in dopaminergic neurons.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2013.12.064DOI Listing

Publication Analysis

Top Keywords

cell death
28
dopaminergic neuronal
12
neuronal cell
12
cell
10
autophagy
8
mitophagy autophagy
8
dopaminergic cell
8
autophagy mitophagy
8
staurosporine treatment
8
dopaminergic
7

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!