Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

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

References

  • Altman SA, Randers L, Rao G (1993) Comparison of trypan blue dye exclusion and fluorometric assays for mammalian cell viability determinations. Biotechnol Prog 9:671–674

    CAS  PubMed  Google Scholar 

  • Benard G, Trian T, Bellance N, Berger P, Lavie J, Espil-Taris C, Rocher C, Eimer-Bouillot S, Goizet C, Nouette-Gaulain K (2013) Adaptative capacity of mitochondrial biogenesis and of mitochondrial dynamics in response to pathogenic respiratory chain dysfunction. Antioxid Redox Signal 19:350–365

    CAS  PubMed  Google Scholar 

  • Bezprozvanny I (2009) Calcium signaling and neurodegenerative diseases. Trends Mol Med 15:89–100

    CAS  PubMed  PubMed Central  Google Scholar 

  • Birkenmeier EH, Gwynn B, Howard S, Jerry J, Gordon JI, Landschulz WH, McKnight SL (1989) Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev 3:1146–1156

    CAS  PubMed  Google Scholar 

  • Blandini F, Armentero MT (2012) Animal models of Parkinson’s disease. FEBS J 279:1156–1166

    CAS  PubMed  Google Scholar 

  • Bown CD, Wang J-F, Young LT (2000) Increased expression of endoplasmic reticulum stress proteins following chronic valproate treatment of rat C6 glioma cells. Neuropharmacology 39:2162–2169

    CAS  PubMed  Google Scholar 

  • Boyce M, Yuan J (2006) Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13:363–373

    CAS  PubMed  Google Scholar 

  • Brand MD, Nicholls DG (2011) Assessing mitochondrial dysfunction in cells. Biochem J 435:297–312

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cai P, Ye J, Zhu J, Liu D, Chen D, Wei X, Johnson NR, Wang Z, Zhang H, Cao G (2016) Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effect of bFGF in the 6-OHDA-induced Parkinson’s disease model. Aging Dis 7:336–449

    PubMed  PubMed Central  Google Scholar 

  • Chalmers-Redman RM, Fraser ADM, Carlile GW, Pong A, Tatton WG (1999) Glucose protection from MPP+-induced apoptosis depends on mitochondrial membrane potential and ATP synthase. Biochem Biophys Res Commun 257:440–447

    CAS  PubMed  Google Scholar 

  • Chaudhuri AD, Kabaria S, Choi DC, Mouradian MM, Junn E (2015) MicroRNA-7 promotes glycolysis to protect against 1-methyl-4-phenylpyridinium-induced cell death. J Biol Chem 290:12425–12434

    CAS  PubMed  PubMed Central  Google Scholar 

  • Choi AY, Choi JH, Yoon H, Hwang K-Y, Noh MH, Choe W, Yoon K-S, Ha J, Yeo E-J, Kang I (2011) Luteolin induces apoptosis through endoplasmic reticulum stress and mitochondrial dysfunction in Neuro-2a mouse neuroblastoma cells. Eur J Pharmacol 668:115–126

    CAS  PubMed  Google Scholar 

  • Conn KJ, Gao WW, Ullman MD, McKeon-O'Malley C, Eisenhauer PB, Fine RE, Wells JM (2002) Specific up-regulation of GADD153/CHOP in 1-methyl-4-phenyl-pyridinium-treated SH-SY5Y cells. J Neurosci Res 68:755–760

    CAS  PubMed  Google Scholar 

  • Couch JF (1943) Rutin for the capillaries. Yearbook of agriculture, pp 711–715

  • Egawa N, Yamamoto K, Inoue H, Hikawa R, Nishi K, Mori K, Takahashi R (2011) The endoplasmic reticulum stress sensor, ATF6α, protects against neurotoxin-induced dopaminergic neuronal death. J Biol Chem 286:7947–7957

    CAS  PubMed  Google Scholar 

  • Germain M, Nguyen AP, Khacho M, Patten DA, Screaton RA, Park DS, Slack RS (2012) LKB1-regulated adaptive mechanisms are essential for neuronal survival following mitochondrial dysfunction. Hum Mol Genet 22:952–962

    PubMed  Google Scholar 

  • Ghorbani A (2017) Mechanisms of antidiabetic effects of flavonoid rutin. Biomed Pharmacother 96:305–312

    CAS  PubMed  Google Scholar 

  • Ghribi O, Herman MM, Pramoonjago P, Savory J (2003) MPP+ induces the endoplasmic reticulum stress response in rabbit brain involving activation of the ATF-6 and NF-κB signaling pathways. J Neuropathol Exp Neurol 62:1144–1153

    CAS  PubMed  Google Scholar 

  • Gorbatyuk MS, Gorbatyuk OS (2013) The molecular chaperone GRP78/BiP as a therapeutic target for neurodegenerative disorders: a mini review. J Genet Syndr Gene Ther 4:128

    PubMed  PubMed Central  Google Scholar 

  • Guardia T, Rotelli AE, Juarez AO, Pelzer LE (2001) Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. II Farmaco 56:683–687

    CAS  Google Scholar 

  • Hang L, Thundyil J, Lim KL (2015) Mitochondrial dysfunction and Parkinson disease: a Parkin–AMPK alliance in neuroprotection. Ann N Y Acad Sci 1350:37–47

    CAS  PubMed  Google Scholar 

  • Hao W, Chang C-PB, Tsao C-C, Xu J (2010) Oligomycin-induced bioenergetic adaptation in cancer cells with heterogeneous bioenergetic organization. J Biol Chem 285:12647–12654

    CAS  PubMed  PubMed Central  Google Scholar 

  • Harding HP, Calfon M, Urano F, Novoa I, Ron D (2002) Transcriptional and translational control in the mammalian unfolded protein response. Annu Rev Cell Dev Biol 18:575–599

    CAS  PubMed  Google Scholar 

  • Hill BG, Dranka BP, Zou L, Chatham JC, Darley-Usmar VM (2009) Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J 424:99–107

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hiller MM, Finger A, Schweiger M, Wolf DH (1996) ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway. Science 273:1725–1728

    CAS  PubMed  Google Scholar 

  • Holtz WA, O'Malley KL (2003) Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J Biol Chem 278:19367–19377

    CAS  PubMed  Google Scholar 

  • Hong CT, Chau K-Y, Schapira AH (2016) Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models. Sci Rep 6:25344

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ito K, Eguchi Y, Imagawa Y, Akai S, Mochizuki H, Tsujimoto Y (2017) MPP+ induces necrostatin-1-and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells. Cell Death Dis 3:17013

    Google Scholar 

  • Kaufman RJ (1999) Molecular chaperones and the heat shock response: Sponsored by Cold Spring Harbor Laboratory, 6–10 May 1998. Biochim Biophys Acta Rev Cancer 1423:R13–R27

    CAS  Google Scholar 

  • Keuper M, Jastroch M, Yi C-X, Fischer-Posovszky P, Wabitsch M, Tschöp MH, Hofmann SM (2014) Spare mitochondrial respiratory capacity permits human adipocytes to maintain ATP homeostasis under hypoglycemic conditions. FASEB J 28:761–770

    CAS  PubMed  Google Scholar 

  • Koopman WJ, Nijtmans LG, Dieteren CE, Roestenberg P, Valsecchi F, Smeitink JA, Willems PH (2010) Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation. Antioxid Redox Signal 12:1431–1470

    CAS  PubMed  Google Scholar 

  • Koopman WJ, Willems PH, Smeitink JA (2012) Monogenic mitochondrial disorders. N Engl J Med 366:1132–1141

    CAS  PubMed  Google Scholar 

  • Koopman WJ, Distelmaier F, Smeitink JA, Willems PH (2013) OXPHOS mutations and neurodegeneration. EMBO J 32:9–29

    CAS  PubMed  Google Scholar 

  • Korecka JA, van Kesteren RE, Blaas E, Spitzer SO, Kamstra JH, Smit AB, Swaab DF, Verhaagen J, Bossers K (2013) Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One 8:e63862

    CAS  PubMed  PubMed Central  Google Scholar 

  • Koyano F, Okatsu K, Ishigaki S, Fujioka Y, Kimura M, Sobue G, Tanaka K, Matsuda N (2013) The principal PINK1 and Parkin cellular events triggered in response to dissipation of mitochondrial membrane potential occur in primary neurons. Genes Cells 18:672–681

    CAS  PubMed  PubMed Central  Google Scholar 

  • La Casa C, Villegas I, De La Lastra CA, Motilva V, Calero MM (2000) Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol 71:45–53

    PubMed  Google Scholar 

  • Li X-x, He G-r, Mu X, Xu B, Tian S, Yu X, Meng F-r, Xuan Z-h, Du G-h (2012) Protective effects of baicalein against rotenone-induced neurotoxicity in PC12 cells and isolated rat brain mitochondria. Eur J Pharmacol 674:227–233

    CAS  PubMed  Google Scholar 

  • Lopes FM, Schröder R, da Frota Júnior MLC, Zanotto-Filho A, Müller CB, Pires AS, Meurer RT, Colpo GD, Gelain DP, Kapczinski F (2010) Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies. Brain Res 1337:85–94

    CAS  PubMed  Google Scholar 

  • Lowenstein DH, Chan PH, Miles MF (1991) The stress protein response in cultured neurons: characterization and evidence for a protective role in excitotoxicity. Neuron 7:1053–1060

    CAS  PubMed  Google Scholar 

  • Lu T-H, Tseng T-J, Su C-C, Tang F-C, Yen C-C, Liu Y-Y, Yang C-Y, Wu C-C, Chen K-L, Hung D-Z (2014) Arsenic induces reactive oxygen species-caused neuronal cell apoptosis through JNK/ERK-mediated mitochondria-dependent and GRP 78/CHOP-regulated pathways. Toxicol Lett 224:130–140

    CAS  PubMed  Google Scholar 

  • Magalingam KB, Radhakrishnan A, Haleagrahara N (2013) Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. Int J Mol Med 32:235–240

    CAS  PubMed  Google Scholar 

  • Magalingam KB, Radhakrishnan A, Haleagrahara N (2016) Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells. Int J Immunopathol Pharmacol 29:30–39

    CAS  PubMed  Google Scholar 

  • Maruoka N, Murata T, Omata N, Takashima Y, Fujibayashi Y, Wada Y (2007) Biphasic mechanism of the toxicity induced by 1-methyl-4-phenylpyridinium ion (MPP+) as revealed by dynamic changes in glucose metabolism in rat brain slices. Neurotoxicology 28:672–678

    CAS  PubMed  Google Scholar 

  • Mazzio E, Soliman K (2003) D-(+)-glucose rescue against 1-methyl-4-phenylpyridinium toxicity through anaerobic glycolysis in neuroblastoma cells. Brain Res 962:48–60

    CAS  PubMed  Google Scholar 

  • McCoy MK, Cookson MR (2012) Mitochondrial quality control and dynamics in Parkinson’s disease. Antioxid Redox Signal 16:869–882

    CAS  PubMed  PubMed Central  Google Scholar 

  • Michel PP, Toulorge D, Guerreiro S, Hirsch EC (2013) Specific needs of dopamine neurons for stimulation in order to survive: implication for Parkinson disease. FASEB J 27:3414–3423

    CAS  PubMed  Google Scholar 

  • Nicholls D, Ferguson S (2013) Bioenergetics, vol 4. Academic, Norwell

    Google Scholar 

  • Oyadomari S, Takeda K, Takiguchi M, Gotoh T, Matsumoto M, Wada I, Akira S, Araki E, Mori M (2001) Nitric oxide-induced apoptosis in pancreatic β cells is mediated by the endoplasmic reticulum stress pathway. Proc Natl Acad Sci 98:10845–10850

    CAS  PubMed  Google Scholar 

  • Ozawa S, Ueda S, Imamura H, Mori K, Asanuma K, Yanagita M, Nakagawa T (2015) Glycolysis, but not mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes. Sci Rep 5:18575

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park A, Stacy M (2009) Non-motor symptoms in Parkinson’s disease. J Neurol 256:293–298

    PubMed  Google Scholar 

  • Park S-E, Sapkota K, Choi J-H, Kim M-K, Kim YH, Kim KM, Kim KJ, Oh H-N, Kim S-J, Kim S (2014) Rutin from Dendropanax morbifera Leveille protects human dopaminergic cells against rotenone induced cell injury through inhibiting JNK and p38 MAPK signaling. Neurochem Res 39:707–718

    CAS  PubMed  Google Scholar 

  • Paschen W, Mengesdorf T (2005) Endoplasmic reticulum stress response and neurodegeneration. Cell Calcium 38:409–415

    CAS  PubMed  Google Scholar 

  • Pelletier M, Billingham LK, Ramaswamy M, Siegel RM (2014) Extracellular flux analysis to monitor glycolytic rates and mitochondrial oxygen consumption. In: Methods Enzymol. Elsevier, Amsterdam, pp 125–149

    Google Scholar 

  • Perk AA, Shatynska-Mytsyk I, Gerçek YC, Boztaş K, Yazgan M, Fayyaz S, Farooqi AA (2014) Rutin mediated targeting of signaling machinery in cancer cells. Cancer Cell Int 14(1):124

    PubMed  PubMed Central  Google Scholar 

  • Petersen OH, Michalak M, Verkhratsky A (2005) Calcium signalling: past, present and future. Cell Calcium 38:161–169

    CAS  PubMed  Google Scholar 

  • Pringsheim T, Jette N, Frolkis A, Steeves TD (2014) The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 29:1583–1590

    PubMed  Google Scholar 

  • Ravid R, Ferrer I (2012) Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson’s disease. FEBS J 279:1167–1176

    CAS  PubMed  Google Scholar 

  • Requejo-Aguilar R, Bolaños JP (2016) Mitochondrial control of cell bioenergetics in Parkinson’s disease. Free Radic Biol Med 100:123–137

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ryu EJ, Harding HP, Angelastro JM, Vitolo OV, Ron D, Greene LA (2002) Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson’s disease. J Neurosci 22:10690–10698

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schapira A, Cooper J, Dexter D, Clark J, Jenner P, Marsden C (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54:823–827

    CAS  PubMed  Google Scholar 

  • Smiley ST, Reers M, Mottola-Hartshorn C, Lin M, Chen A, Smith TW, Steele G, Chen LB (1991) Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci 88:3671–3675

    CAS  PubMed  Google Scholar 

  • Song J-X, Shaw P-C, Sze C-W, Tong Y, Yao X-S, Ng T-B, Zhang Y-B (2010) Chrysotoxine, a novel bibenzyl compound, inhibits 6-hydroxydopamine induced apoptosis in SH-SY5Y cells via mitochondria protection and NF-κB modulation. Neurochem Int 57:676–689

    CAS  PubMed  Google Scholar 

  • Surmeier DJ, Schumacker PT (2013) Calcium, bioenergetics, and neuronal vulnerability in Parkinson’s disease. J Biol Chem 288:10736–10741

    CAS  Google Scholar 

  • Surmeier DJ, Guzman JN, Sanchez J, Schumacker PT (2012) Physiological phenotype and vulnerability in Parkinson’s disease. Cold Spring Harb Perspect Med 2:a009290

    PubMed  PubMed Central  Google Scholar 

  • Umek RM, Friedman AD, McKnight SL (1991) CCAAT-enhancer binding protein: a component of a differentiation switch. Science 251:288–292

    CAS  PubMed  Google Scholar 

  • Van der Merwe C, Van Dyk HC, Engelbrecht L, van der Westhuizen FH, Kinnear C, Loos B, Bardien S (2017) Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson’s disease from mitochondrial dysfunction and cell death. Mol Neurobiol 54:2752–2762

    PubMed  Google Scholar 

  • Wang X-J, Xu J-X (2005) Salvianic acid A protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity. Neurosci Res 51:129–138

    CAS  PubMed  Google Scholar 

  • Wang X-Z, Lawson B, Brewer JW, Zinszner H, Sanjay A, Mi L-J, Boorstein R, Kreibich G, Hendershot LM, Ron D (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol Cell Biol 16:4273–4280

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J-F, Bown C, Young LT (1999) Differential display PCR reveals novel targets for the mood-stabilizing drug valproate including the molecular chaperone GRP78. Mol Pharmacol 55:521–527

    CAS  PubMed  Google Scholar 

  • Wang B, Su C-J, Feng Y, Zhou Y, Huang Y, Wang Z-H, Luo W-F, Chen L-H, Liu T, Liu T-T (2018) The neuroprotection of low-dose morphine in cellular and animal models of Parkinson's disease through ameliorating endoplasmic reticulum (ER) stress and activating autophagy. Front Mol Neurosci 11:120

    PubMed  PubMed Central  Google Scholar 

  • Webster R, Gawde M, Bhattacharya R (1996) Protective effect of rutin, a flavonol glycoside, on the carcinogen-induced DNA damage and repair enzymes in rats. Cancer Lett 109:185–191

    CAS  PubMed  Google Scholar 

  • Xie H-r, Hu L-s, Li G-y (2010) SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson’s disease. Chin Med J 123:1086–1092

    CAS  PubMed  Google Scholar 

  • Yamamoto H, Morino K, Mengistu L, Ishibashi T, Kiriyama K, Ikami T, Maegawa H (2016) Amla enhances mitochondrial spare respiratory capacity by increasing mitochondrial biogenesis and antioxidant systems in a murine skeletal muscle cell line. Oxidative Med Cell Longev 2016:1–11

    CAS  Google Scholar 

  • Yang J, Guo J, Yuan J (2008) In vitro antioxidant properties of rutin. LWT-Food Science and Technology 41:1060–1066

    CAS  Google Scholar 

  • Yoo H, Ku S-K, Baek Y-D, Bae J-S (2014) Anti-inflammatory effects of rutin on HMGB1-induced inflammatory responses in vitro and in vivo. Inflamm Res 63:197–206

    CAS  PubMed  Google Scholar 

  • Yu Z, Luo H, Fu W, Mattson MP (1999) The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol 155:302–314

    CAS  PubMed  Google Scholar 

  • Zaichick SV, McGrath KM, Caraveo G (2017) The role of Ca2+ signaling in Parkinson’s disease. Dis Model Mech 10:519–535

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Q, Yang X, Cai D, Ye L, Hou Y, Zhang L, Cheng J, Shen Y, Wang K, Bai Y (2016) Echinacoside protects against MPP+-induced neuronal apoptosis via ros/atf3/chop pathway regulation. Neurosci Bull 32:349–362

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Medical Biosciences, University of the Western Cape, Robert Sobukwe Road, Private Bag X17, Bellville, 7535, South Africa

    Adaze Bijou Enogieru, Donavon Charles Hiss & Okobi Eko Ekpo

  2. Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    William Lloyd Haylett

  3. Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    William Lloyd Haylett

  4. Focus Area for Human Metabolomics, Faculty of Natural Sciences, North-West University, Potchefstroom, South Africa

    Hayley Christy Miller & Francois Hendrikus van der Westhuizen

Authors
  1. Adaze Bijou Enogieru
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William Lloyd Haylett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hayley Christy Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francois Hendrikus van der Westhuizen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Donavon Charles Hiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Okobi Eko Ekpo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Okobi Eko Ekpo.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights

• Rutin protects against dysregulated Ca2+ homeostasis in SH-SY5Y cells treated with MPP+.

• Rutin maintains mitochondrial membrane potential in SH-SY5Y cells treated with MPP+.

• The protective effect of rutin against MPP+-induced toxicity involves the inhibition of ER stress.

• Rutin mitigates impaired oxidative phosphorylation in SH-SY5Y cells treated with MPP+.

• Rutin improves glycolysis in SH-SY5Y cells treated with MPP+.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Enogieru, A.B., Haylett, W.L., Miller, H.C. et al. Attenuation of Endoplasmic Reticulum Stress, Impaired Calcium Homeostasis, and Altered Bioenergetic Functions in MPP+-Exposed SH-SY5Y Cells Pretreated with Rutin. Neurotox Res 36, 764–776 (2019). https://doi.org/10.1007/s12640-019-00048-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-019-00048-4

Keywords

Search

Navigation