Hydrogen peroxide-reducing factor released by PC12D cells increases cell tolerance against oxidative stress

Asami Muraishi, Emi Haneta, Yoshiro Saito, Yutaka Hitomi, Mamoru Sano, Noriko Noguchi

Research output: Contribution to journalArticlepeer-review


PC12D cells, a subline of rat adrenal pheochromocytoma PC12 cells, extend neurites rapidly in response to differentiation stimuli and are used to investigate the molecular mechanisms of neurite extension. In the present study, we found significant tolerance of PC12D cells against Parkinson’s disease-related stimuli such as dopamine and 6-hydroxydopamine; this tolerance was significantly decreased by a change in the medium. Conditioned medium from PC12D cells induced tolerance against oxidative stress, which suggests that cytoprotective factor may be released by PC12D cells into the culture medium. Conditioned medium-induced tolerance was not found for PC12 cells or human neuroblastoma SH-SY5Y cells. A cytoprotective factor generated by PC12D cells exhibited hydrogen peroxide-reducing activity. Chemical characterization showed that this cytoprotective factor is water soluble and has a molecular weight about 1000Da, and that its activity is inhibited by sodium cyanide. Release of this cytoprotective factor was increased by differentiation stimuli and oxidative stress. Taken together, these results suggest that release of a hydrogen peroxide-reducing factor by PC12D cells increases cell tolerance against oxidative stress. This study provides new insights into the antioxidative properties of factors in extracellular fluid.

Original languageEnglish
Pages (from-to)777-785
Number of pages9
JournalBiological and Pharmaceutical Bulletin
Issue number5
Publication statusPublished - 2018
Externally publishedYes


  • Cytoprotective factor
  • Extracellular fluid
  • Hydrogen peroxide
  • Low molecular compound
  • PC12D cell

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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