Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation

Bhavana Chhunchha, Nigar Fatma, Eri Kubo, Prerana Rai, Sanjay Singh, Dhirendra P. Singh

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Oxidative stress and endoplasmic reticulum (ER) stress are emerging as crucial events in the etiopathology of many neurodegenerative diseases. While the neuroprotective contributions of the dietary compound curcumin has been recognized, the molecular mechanisms underlying curcumin's neuroprotection under oxidative and ER stresses remains elusive. Herein, we show that curcumin protects HT22 from oxidative and ER stresses evoked by the hypoxia (1% O2 or CoCl2 treatment) by enhancing peroxiredoxin 6 (Prdx6) expression. Cells exposed to CoCl2 displayed reduced expression of Prdx6 with higher reactive oxygen species (ROS) expression and activation of NF-κB with IκB phosphorylation. When NF-κB activity was blocked by using SN50, an inhibitor of NF-κB, or cells treated with curcumin, the repression of Prdx6 expression was restored, suggesting the involvement of NF-κB in modulating Prdx6 expression. These cells were enriched with an accumulation of ER stress proteins, C/EBP homologous protein (CHOP), GRP/78, and calreticulin, and had activated states of caspases 12, 9, and 3. Reinforced expression of Prdx6 in HT22 cells by curcumin reestablished survival signaling by reducing propagation of ROS and blunting ER stress signaling. Intriguingly, knockdown of Prdx6 by antisense revealed that loss of Prdx6 contributed to cell death by sustaining enhanced levels of ER stress-responsive proapoptotic proteins, which was due to elevated ROS production, suggesting that Prdx6 deficiency is a cause of initiation of ROS-mediated ER stress-induced apoptosis. We propose that using curcumin to reinforce the naturally occurring Prdx6 expression and attenuate ROS-based ER stress and NF-κB-mediated aberrant signaling improves cell survival and may provide an avenue to treat and/or postpone diseases associated with ROS or ER stress.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume304
Issue number7
DOIs
StatePublished - Apr 1 2013

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Peroxiredoxin VI
Endoplasmic Reticulum Stress
Curcumin
Oxidative Stress
Cell Death
Reactive Oxygen Species
Transcription Factor CHOP
Caspase 12
Calreticulin
Hypoxia
Caspase 9
Heat-Shock Proteins
Protein C
Caspase 3
Neurodegenerative Diseases
Cell Survival

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Physiology
  • Medicine(all)

Cite this

Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation. / Chhunchha, Bhavana; Fatma, Nigar; Kubo, Eri; Rai, Prerana; Singh, Sanjay; Singh, Dhirendra P.

In: American Journal of Physiology - Cell Physiology, Vol. 304, No. 7, 01.04.2013.

Research output: Contribution to journalArticle

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