The autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress

Ken Hayashi, Katsuaki Dan, Fumiyuki Goto, Nana Tshuchihashi, Yasuyuki Nomura, Masato Fujioka, Sho Kanzaki, Kaoru Ogawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The main purposes of our study were to consider the effect of autophagy on auditory cells under oxidative stress, and the function of possible crosstalk among p62, Keap1 and Nrf2 in autophagy-deficient auditory cells. First, we described how cell death was induced in auditory cell line (HEI-OC1) exposed to H2O2. We found that the decision for the cell death of auditory cells under oxidative stress depends on the balance between autophagy and necrosis due to ATP depletion, and autophagy plays a cytoprotective function in oxidative stress-induced necrosis. Our data clearly suggested that autophagy was a cell survival mechanism in H2O2-induced cell death, based on the observation that suppression of autophagy by knockdown of Atg7 sensitized, whereas activation of autophagy by rapamycin protected against H2O2-induced cell death. Next, our results regarding the relationship among p62, Nrf2 and Keap1 by siRNA paradoxically showed that p62 creates a positive feedback loop in the Keap1/Nrf2 pathway. Autophagy impaired by Atg7 knockdown degrades Keap1 in a p62-dependent manner, whereas Nrf2 is activated. As a result, the cell death induced by H2O2 was promoted in auditory cells. Taken together, these results suggested that the autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress.

Original languageEnglish
Pages (from-to)382-393
Number of pages12
JournalCellular Signalling
Volume27
Issue number2
DOIs
Publication statusPublished - 2015 Feb 1

Fingerprint

Autophagy
Oxidative Stress
Cell Death
Necrosis
Sirolimus
Small Interfering RNA
Cell Survival
Adenosine Triphosphate
Cell Line

Keywords

  • Auditory cell
  • Autophagy
  • Keap1/Nrf2
  • Oxidative stress
  • P62

ASJC Scopus subject areas

  • Cell Biology

Cite this

The autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress. / Hayashi, Ken; Dan, Katsuaki; Goto, Fumiyuki; Tshuchihashi, Nana; Nomura, Yasuyuki; Fujioka, Masato; Kanzaki, Sho; Ogawa, Kaoru.

In: Cellular Signalling, Vol. 27, No. 2, 01.02.2015, p. 382-393.

Research output: Contribution to journalArticle

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