Brodnanova 2021 Eur J Pharmacol

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Brodnanova M, Hatokova Z, Evinova A, Cibulka M, Racay P (2021) Differential impact of imipramine on thapsigargin- and tunicamycin-induced endoplasmic reticulum stress and mitochondrial dysfunction in neuroblastoma SH-SY5Y cells. Eur J Pharmacol 902:174073.

Β» PMID: 33798597 Open Access

Brodnanova Maria, Hatokova Zuzana, Evinova Andrea, Cibulka Michal, Racay Peter (2021) Eur J Pharmacol

Abstract: The aim of our work was to study effect of antidepressant imipramine on both thapsigargin- and tunicamycin-induced ER stress and mitochondrial dysfunction in neuroblastoma SH-SY5Y cells. ER stress in SH-SY5Y cells was induced by either tunicamycin or thapsigargin in the presence or absence of imipramine. Cell viability was tested by the MTT assay. Splicing of XBP1 mRNA was studied by RT-PCR. Finally, expression of Hrd1 and Hsp60 was determined by Western blot analysis.

Our findings provide evidence that at high concentrations imipramine potentiates ER stress-induced death of SH-SY5Y cells. The effect of imipramine on ER stress-induced death of SH-SY5Y cells was stronger in combination of imipramine with thapsigargin. In addition, we have found that treatment of SH-SY5Y cells with imipramine in combination of either thapsigargin or tunicamycin is associated with the alteration of ER stress-induced IRE1Ξ±-XBP1 signalling. Despite potentiation of ER stress-induced XBP1 splicing, imipramine suppresses both thapsigargin- and tunicamycin-induced expression of Hrd1. Finally, imipramine in combination with thapsigargin, but not tunicamycin, aggravates ER stress-induced mitochondrial dysfunction without significant impact on intracellular mitochondrial content as indicated by the unaltered expression of Hsp60.

Our results indicate the possibility that chronic treatment with imipramine might be associated with a higher risk of development and progression of neurodegenerative disorders, in particular those allied with ER stress and mitochondrial dysfunction like Parkinson's and Alzheimer's disease. β€’ Keywords: Cell death, Endoplasmic reticulum, Imipramine, Mitochondria, Neurodegenerative disorders, Unfolded protein response β€’ Bioblast editor: Reiswig R


Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Cell death  Organism: Human  Tissue;cell: Neuroblastoma  Preparation: Permeabilized cells, Intact cells 


Coupling state: LEAK, ROUTINE, ET  Pathway: N, S, ROX  HRR: Oxygraph-2k 

2021-07 


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