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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

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

Abstract Source:

Biol Trace Elem Res. 2015 Nov 7. Epub 2015 Nov 7. PMID: 26546554

Abstract Author(s):

Syed Husain Mustafa Rizvi, Arshiya Parveen, Israr Ahmad, Iqbal Ahmad, Anoop K Verma, Md Arshad, Abbas Ali Mahdi

Article Affiliation:

Syed Husain Mustafa Rizvi

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.

Study Type : In Vitro Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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