title: 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.
authors: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors: Kyo
authors: K
authors: Shirai
authors: Tatsumi
authors: T
authors: Okada
authors: Kanako
authors: K
authors: Konishi
authors: Hiroshi
authors: H
authors: Murata
authors: Soichiro
authors: S
authors: Akashi
authors: Fumio
authors: F
authors: Sugawara
authors: Nobuo
authors: N
authors: Watanabe
authors: Takao
authors: T
authors: Arai
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000737:chemistry*; D003545:Cysteine / Q000494:pharmacology; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008954:Models, Biological; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D017693:Sodium Bicarbonate / Q000737:chemistry; D012972:Sodium Hydroxide / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001639:Bicarbonates; D003470:Culture Media; D013438:Sulfhydryl Compounds; D012972:Sodium Hydroxide; C002385:linsidomine; D017693:Sodium Bicarbonate; D008981:Molsidomine; D005978:Glutathione; D003545:Cysteine