Biological Trace Element Research

, Volume 172, Issue 1, pp 108–119 | Cite as

Aluminum Activates PERK-EIF2α Signaling and Inflammatory Proteins in Human Neuroblastoma SH-SY5Y Cells

  • Syed Husain Mustafa Rizvi
  • Arshiya Parveen
  • Israr Ahmad
  • Iqbal Ahmad
  • Anoop K. Verma
  • Md. Arshad
  • Abbas Ali MahdiEmail author


Aluminum is the third most abundant element present in the earth’s crust and human exposure to it is possible due to industrialization, utensils, medicines, antiperspirants, etc. Evidences suggest involvement of aluminum in a variety of neurodegenerative disorders including Alzheimer’s disease. Endoplasmic reticulum (ER) stress has been implicated in various neurological disorders. ER stress may be a result of impaired calcium homeostasis due to perturbed redox balance and is known to elicit inflammation through the activation of unfolded protein response (UPR). In the present study, we aimed to investigate the role of aluminum in ER stress-mediated activation of inflammatory responses in neuroblastoma cells. Lactate dehydrogenase (LDH) release assay revealed that aluminum compromised the membrane integrity of neuroblastoma cells, probably due to membrane damage, as indicated by enhanced levels of lipid peroxidation (LPO). Besides this, our results clearly demonstrated elevated reactive oxygen species (ROS) levels and a weakened antioxidant defence system manifested by decrease in catalase (CAT) activity and cellular glutathione (GSH). Moreover, we studied the expression of key apoptosis-related proteins, ER stress-mediated activation of UPR, and its downstream inflammatory pathway. It was observed that aluminum potentially enhanced protein levels of PERK, EIF2α, caspase 9, caspase 3, and inflammatory markers like NF-κB, NLRP3, HMGB1, and nitric oxide (NO). Furthermore, aluminum altered TNFα, IL1β, IL6, and IL10 mRNA levels as well. The overall findings indicated that aluminum mediates UPR activation through ER stress, which results in induction of inflammatory pathway and apoptotic proteins in neuronal cells.


ER stress Unfolded protein response Oxidative stress Inflammation 



This work was supported by Indian Council of Medical Research (ICMR) [Project No.45/6/2013 BIO/BMS]. We are grateful to Indian Council of Medical Research (ICMR) for award of fellowship to SHMR.

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 2015

Authors and Affiliations

  • Syed Husain Mustafa Rizvi
    • 1
  • Arshiya Parveen
    • 1
  • Israr Ahmad
    • 1
  • Iqbal Ahmad
    • 2
  • Anoop K. Verma
    • 1
  • Md. Arshad
    • 3
  • Abbas Ali Mahdi
    • 1
    Email author
  1. 1.Department of Biochemistry and Forensic Medicine & ToxicologyKing George’s Medical UniversityLucknowIndia
  2. 2.Fibre Toxicology DivisionCSIR-Indian Institute of Toxicology ResearchLucknowIndia
  3. 3.Department of ZoologyLucknow UniversityLucknowIndia

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