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

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.

journal_name

Oxid Med Cell Longev

journal_title

Oxidative medicine and cellular longevity

authors

Shirai K,Okada T,Konishi K,Murata H,Akashi S,Sugawara F,Watanabe N,Arai T

doi

10.1155/2012/326731

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

326731

eissn

1942-0900

issn

1942-0994

journal_volume

2012

pub_type

杂志文章

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