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Neurotoxicity Research

, Volume 32, Issue 3, pp 351–361 | Cite as

Autophagy Activation Alleviates Amyloid-β-Induced Oxidative Stress, Apoptosis and Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells

  • Abhishek Kumar SinghEmail author
  • Akalabya Bissoyi
  • Mahendra Pratap Kashyap
  • Pradeep Kumar Patra
  • Syed Ibrahim Rizvi
ORIGINAL ARTICLE

Abstract

Autophagy is an evolutionary conserved catabolic process that ensures continuous removal of damaged cell organelles and long-lived protein aggregates to maintain cellular homeostasis. Although autophagy has been implicated in amyloid-β (Aβ) production and deposition, its role in pathogenesis of Alzheimer’s disease remains elusive. Thus, the present study was undertaken to assess the cytoprotective and neuroprotective potential of autophagy on Aβ-induced oxidative stress, apoptosis and neurotoxicity in human neuroblastoma SH-SY5Y cells. The treatment of Aβ1-42 impaired the cell growth and redox balance, and induced apoptosis and neurotoxicity in SH-SY5Y cells. Next, the treatment of rapamycin (RAP) significantly elevated the expression of autophagy markers such as microtubule-associated protein-1 light chain-3 (LC3), sequestosome-1/p62, Beclin-1, and unc-51-like kinase-1 (ULK1) in SH-SY5Y cells. RAP-induced activation of autophagy notably alleviated the Aβ1-42-induced impairment of redox balance by decreasing the levels of pro-oxidants such as reactive oxygen species, lipid peroxidation and Ca2+ influx, and concurrently increasing the levels of antioxidant enzymes such as superoxide dismutase and catalase. The RAP-induced autophagy also ameliorated Aβ1-42-induced loss of mitochondrial membrane potential and apoptosis. Additionally, the activated autophagy provided significant neuroprotection against Aβ1-42-induced neurotoxicity by elevating the expression of neuronal markers such as synapsin-I, PSD95, NCAM, and CREB. However, 3-methyladenine treatment significantly exacerbated the neurotoxic effects of Aβ1-42. Taken together, our study demonstrated that the activation of autophagy provided possible neuroprotection against Aβ-induced cytotoxicity, oxidative stress, apoptosis, and neurotoxicity in SH-SY5Y neuronal cells.

Keywords

Amyloid-beta Autophagy Neuroblastoma SH-SY5Y cells Neuroprotection Oxidative stress Rapamycin 3-Methyladenine 

Notes

Acknowledgements

Dr. D. S. Kotahri Post Doctoral Fellowship scheme of University Grants Commission, New Delhi, India, is acknowledged for providing financial support (F.4-2/2006(BSR)/BL/14-15/0326) and fellowship to A. K. Singh.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Abhishek Kumar Singh
    • 1
    Email author
  • Akalabya Bissoyi
    • 2
  • Mahendra Pratap Kashyap
    • 3
  • Pradeep Kumar Patra
    • 4
  • Syed Ibrahim Rizvi
    • 1
  1. 1.Department of BiochemistryUniversity of AllahabadAllahabadIndia
  2. 2.Department of Biomedical EngineeringNational Institute of TechnologyRaipurIndia
  3. 3.Department of UrologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of BiochemistryPt. JNM Medical CollegeRaipurIndia

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