Inhibition of NO-induced β-cell death by novel NF-κB inhibitor (-)-DHMEQ via activation of Nrf2-ARE pathway

Akira Ogasawara, Siro Simizu, Ayumi Ito, Toshihide Kawai, Yoshifumi Saisho, Izumi Takei, Kazuo Umezawa

Research output: Contribution to journalArticle

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Abstract

Excessive nitric oxide (NO) plays a pivotal role in the progression of β-cell apoptosis in type 1 diabetes mellitus. We used mouse insulinoma Min6 cells as a model of β cells in this research. We found that (-)-DHMEQ, an NF-κB inhibitor, rescued β cells from NO-induced apoptosis, and then studied the mechanism of apoptosis inhibition. (-)-DHMEQ activated Nrf2 and induced transcription of Nrf2-target genes following the increase of antioxidant response element (ARE) reporter activity. Similarly, tert-butyl hydroquinone (tBHQ), a known activator of Nrf2, inhibited NO-induced cell death along with the transcriptional activation of ARE. RNAi-mediated knockdown of Nrf2 lowered the cytoprotective effect of (-)-DHMEQ against NO, suggesting that (-)-DHMEQ inhibited NO-induced cell death via Nrf2 activation. Furthermore, overexpression of Nrf2 rendered cells to be more resistant to NO, indicating that Nrf2 activation provides critical defense function against NO in Min6 cells. Taken together, we conclude that (-)-DHMEQ may be a useful therapeutic agent for type 1 diabetes mellitus in the onset of disease by protecting β cells from apoptosis.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume433
Issue number2
DOIs
Publication statusPublished - 2013 Apr

Fingerprint

Antioxidant Response Elements
Cell death
Nitric Oxide
Cell Death
Chemical activation
Apoptosis
Medical problems
Type 1 Diabetes Mellitus
Insulinoma
Transcription
RNA Interference
Transcriptional Activation
Genes

Keywords

  • β Cell
  • (-)-DHMEQ
  • Apoptosis
  • NF-κB
  • Nrf2

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Inhibition of NO-induced β-cell death by novel NF-κB inhibitor (-)-DHMEQ via activation of Nrf2-ARE pathway. / Ogasawara, Akira; Simizu, Siro; Ito, Ayumi; Kawai, Toshihide; Saisho, Yoshifumi; Takei, Izumi; Umezawa, Kazuo.

In: Biochemical and Biophysical Research Communications, Vol. 433, No. 2, 04.2013, p. 181-187.

Research output: Contribution to journalArticle

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