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Neurotoxicity Research

, Volume 36, Issue 4, pp 764–776 | Cite as

Attenuation of Endoplasmic Reticulum Stress, Impaired Calcium Homeostasis, and Altered Bioenergetic Functions in MPP+-Exposed SH-SY5Y Cells Pretreated with Rutin

  • Adaze Bijou Enogieru
  • William Lloyd Haylett
  • Hayley Christy Miller
  • Francois Hendrikus van der Westhuizen
  • Donavon Charles Hiss
  • Okobi Eko EkpoEmail author
Original Article

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder that affects approximately 1% of the population over the age of 65 years. While treatment options for PD are limited, reports show that plant-derived bioactive compounds such as rutin possess numerous pharmacological benefits, including antioxidant and antiapoptotic activities. This study aimed to investigate the potential role of rutin in MPP+-treated SH-SY5Y neuroblastoma cells, an established cell model of PD. Our findings reveal increased concentrations of Ca2+ and endoplasmic reticulum (ER) stress as well as impaired mitochondrial membrane potential and bioenergetic status in SH-SY5Y cells treated with MPP+ only. This is demonstrated by a significant reduction in the expression levels of BiP, significantly reduced basal respiration, maximal respiration, and spare respiratory capacity as well as a significant increase in the expression levels of CHOP; however, these effects were significantly attenuated following pretreatment with rutin. Also, rutin significantly improved basal and compensatory glycolysis as a response to an impaired oxidative phosphorylation system triggered by MPP+, characterized by deficient ATP production. In conclusion, our findings provide the first evidence on the ability of rutin to maintain Ca2+ homeostasis, inhibit ER stress, and protect the mitochondria in MPP+-treated SH-SY5Y cells.

Keywords

Parkinson’s disease Rutin ER stress Oxidative phosphorylation Glycolysis 

Abbreviations

6-OHDA

6-Hydroxydopamine

ATP

Adenosine triphosphate

BiP

Binding immunoglobulin protein

Ca2+

Calcium

CHOP

CCAAT-enhancer-binding protein homologous protein

DMEM

Dulbecco’s modified Eagle medium

ER

Endoplasmic reticulum

FBS

Fetal bovine serum

JC-1

5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbo-cyanine iodide

MMP

Mitochondrial membrane potential

MPP+

1-Methyl-4-phenylpyridinium

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

OXPHOS

Oxidative phosphorylation

PBS

Phosphate-buffered saline

PD

Parkinson’s disease

SEM

Standard error of the mean

SNpc

Substantia nigra pars compacta

UPR

Unfolded protein response

UPS

Ubiquitin proteasome system

Notes

Acknowledgements

We are grateful to the Parkinson’s Disease Research Group, Division of Molecular Biology and Human Genetics, Stellenbosch University, for providing some laboratory materials and workspace needed for this study.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Medical BiosciencesUniversity of the Western CapeBellvilleSouth Africa
  2. 2.Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health SciencesStellenbosch UniversityCape TownSouth Africa
  3. 3.Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health SciencesStellenbosch UniversityCape TownSouth Africa
  4. 4.Focus Area for Human Metabolomics, Faculty of Natural SciencesNorth-West UniversityPotchefstroomSouth Africa

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