Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 655, Issue -, Pages 43-54Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2018.08.007
Keywords
Dopaminergic neurons; A53T alpha-synuclein; Iron; Oxidative stress; Triacylglycerol; Lipid metabolism
Categories
Funding
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT2010-0936, PICT2013-0987]
- CONICET [PIP1122009010068]
- Universidad Nacional del Sur [PGI24B226]
Ask authors/readers for more resources
Pathological alpha-synuclein (alpha-syn) overexpression and iron (Fe)-induced oxidative stress (OS) are involved in the death of dopaminergic neurons in Parkinson's disease (PD). We have previously characterized the role of triacylglycerol (TAG) formation in the neuronal response to Fe-induced OS. In this work we characterize the role of the a-syn variant A53T during Fe-induced injury and investigate whether lipid metabolism has implications for neuronal fate. To this end, we used the N27 dopaminergic neuronal cell line either untransfected (UT) or stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-A53T-alpha-syn (A53T alpha-syn). The overexpression of A53T alpha-syn triggered an increase in TAG content mainly due to the activation of Acyl-CoA synthetase. Since fatty acid (FA) beta-oxidation and phospholipid content did not change in A53T alpha-syn cells, the unique consequence of the increase in FA-CoA derivatives was their acylation in TAG moieties. Control cells exposed to Fe-induced injury displayed increased OS markers and TAG content. Intriguingly, Fe exposure in A53T alpha-syn cells promoted a decrease in OS markers accompanied by a-syn aggregation and elevated TAG content. We report here new evidence of a differential role played by A53T alpha-syn in neuronal lipid metabolism as related to the neuronal response to OS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available