| Title |
Aluminum Activates PERK-EIF2α Signaling and Inflammatory Proteins in Human Neuroblastoma SH-SY5Y Cells
|
|---|---|
| Published in |
Biological Trace Element Research, November 2015
|
| DOI | 10.1007/s12011-015-0553-7 |
| Pubmed ID | |
| Authors |
Syed Husain Mustafa Rizvi, Arshiya Parveen, Israr Ahmad, Iqbal Ahmad, Anoop K. Verma, Md. Arshad, Abbas Ali Mahdi |
| Abstract |
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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 3% |
| Unknown | 31 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 19% |
| Researcher | 4 | 13% |
| Student > Bachelor | 4 | 13% |
| Other | 3 | 9% |
| Lecturer | 2 | 6% |
| Other | 7 | 22% |
| Unknown | 6 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 25% |
| Medicine and Dentistry | 4 | 13% |
| Agricultural and Biological Sciences | 3 | 9% |
| Immunology and Microbiology | 2 | 6% |
| Nursing and Health Professions | 1 | 3% |
| Other | 6 | 19% |
| Unknown | 8 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 February 2018.
All research outputs
#18,430,119
of 22,832,057 outputs
Outputs from Biological Trace Element Research
#1,325
of 2,025 outputs
Outputs of similar age
#205,518
of 285,879 outputs
Outputs of similar age from Biological Trace Element Research
#15
of 27 outputs
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