Bicarbonate plays a critical role in the generation of cytotoxicity during SIN-1 decomposition in culture medium

Kyo Shirai, Tatsumi Okada, Kanako Konishi, Hiroshi Murata, Soichiro Akashi, Fumio Sugawara, Nobuo Watanabe, Takao Arai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

3-Morpholinosydnonimine (SIN-1) is used as a donor of peroxynitrite (ONOO -) in various studies. We demonstrated, however, that, the cell-culture medium remains cytotoxic to PC12 cells even after almost complete SIN-1 decomposition, suggesting that reaction product(s) in the medium, rather than ONOO -, exert cytotoxic effects. Here, we clarified that significant cytotoxicity persists after SIN-1 decomposes in bicarbonate, a component of the culture medium, but not in NaOH. Cytotoxic SIN-1-decomposed bicarbonate, which lacks both oxidizing and nitrosating activities, degrades to innocuous state over time. The extent of SIN-1 cytotoxicity, irrespective of its fresh or decomposed state, appears to depend on the total number of initial SIN-1 molecules per cell, rather than its concentration, and involves oxidative/nitrosative stress-related cell damage. These results suggest that, despite its low abundance, the bicarbonate-dependent cytotoxic substance that accumulates in the medium during SIN-1 breakdown is the cytotoxic entity of SIN-1.

Original languageEnglish
Article number326731
JournalOxidative Medicine and Cellular Longevity
DOIs
Publication statusPublished - 2012 Aug 17

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

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