Format

Send to

Choose Destination
Ann Neurosci. 2018 May;24(4):243-251. doi: 10.1159/000481551. Epub 2017 Oct 30.

1-Methyl-4-Phenylpyridinium-Induced Death of Differentiated SH-SY5Y Neurons Is Potentiated by Cholesterol.

Author information

1
Division of Cell Biology and Physiology, Kolkata, India.
2
Division of Chemistry, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
3
Academy of Scientific and Innovative Research (AcSIR), CSIR Campus, CSIR Road, Taramani, Chennai, India.
4
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, India.
5
Inter University Centre for Biomedical Research and Super Speciality Hospital (IUCBR and SSH), Mahatma Gandhi University Campus at Thalappady, Kottayam, India.

Abstract

Background/Aims:

Hypercholesterolemia is recently considered a risk factor for Parkinson's disease (PD), the most consistent neurodegenerative movement disorder. The study aimed to investigate the effect of exogenous cholesterol on 1-methyl-4-phenylpyridinium (MPP+) parkinsonian neurotoxin-induced cell death, loss of mitochondrial membrane potential, and dopaminergic deficiency in a cellular model of PD.

Methods:

Cholesterol (50 μM) when added in the culture media alone or in combination with MPP+ was studied in SH-SY5Y neuroblastoma cells. There were 4 groups that were studied; SH-SY5Y cells treated with vehicle (control), cells that were treated with 1 mM MPP+ (MPP+), or cholesterol (chol) or both (M + chol). The loss of cell survival was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Dopamine depletion, microtubule-associated protein 2 (MAP-2), and tyrosine hydroxylase (TH)-positive neuronal loss were determined by HPLC-electrochemical detection and TH immunocytochemistry respectively. Mitochondrial membrane potential in cells stained by tetramethylrhodamine methyl ester dye was analysed by flow cytometry.

Results:

Cholesterol treatment potentiated a reduction of neuronal viability with loss of TH-positive neurons in cultures. MPP+-induced depletion of dopamine level in the post-mitotic MAP-2 immunoreactive neurons and loss of mitochondrial membrane potential were also heightened by cholesterol.

Conclusion:

Apparently, changes in neuronal cholesterol content significantly influenced the neurotoxicity and the direct mitochondrial mechanisms involved in MPP+-induced cell death. Our observations demonstrate that high cholesterol incorporated into the differentiated human neuroblastoma cells worsened dopaminergic neuronal survivability through increased depolarization of mitochondrial membrane potential, which is a known mechanism of dopaminergic cell death by MPP+. The present findings support the hypothesis that hypercholesterolemia could be a risk factor for PD.

KEYWORDS:

Cell viability; Cholesterol-induced neuronal death; Dopaminergic neurons; Mitochondrial membrane potential; Tyrosine hydroxylase

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland Icon for PubMed Central
Loading ...
Support Center