Induction of apoptosis by S-nitrosoglutathione and Cu2+ or Ni2+ ion through modulation of bax, bad, and bcl-2 proteins in human colon adenocarcinoma cells
Journal
Molecular Carcinogenesis
Journal Volume
26
Journal Issue
3
Pages
201-211
Date Issued
1999
Author(s)
Abstract
In this study, the amount of S-nitrosoglutathione (GSNO) was measured spectrophotometrically at 334 nm. A spontaneous decrease in absorbency at 334 nm was detected when GSNO was exposed to 37 °C and a high pH (pH 8.0). We investigated the catalytic roles of various metal ions on the decomposition of GSNO. The degradation of GSNO (0.5 mM) was enhanced by the presence of Cu2+ and Ni2+ ions. The amount of nitric oxide (NO) released from GSNO degradation was estimated by the Griess reaction based on nitrite accumulation. The results indicated that nitrite production was elevated at least twofold in the presence of Cu2+. Our study further indicated that Cu2+ enhanced GSNO-induced apoptosis in human colon adenocarcinoma HT 29 cells. We also found that copper ions modulated the expression of bad, bax, and bcl-2 in GSNO-treated HT 29 cells. The levels of bax and bad proteins in treated cells were significantly elevated about fourfold to sixfold when compared with mock-treated cells 24 h after combined treatment with GSNO plus Cu2+ or Ni2+. On the other hand, significant inhibition of bcl-2 occurred in HT 29 cells with simultaneous treatment of GSNO with Cu2+ (or Ni2+). It seemed that Cu2+ and Ni2+ can enhance the decomposition of GSNO, which liberates NO to activate the pathways. Our results demonstrated that the apoptotic effects induced by GSNO were promoted by Ni2+ and Cu2+ through two different mechanisms: depletion of intracellular glutathione and triggering of NO release from GSNO, which then promotes NO-induced apoptosis in human cells.
Subjects
Apoptosis; Bad; Bax; Bcl-2; Copper ion; Nitric oxide
SDGs
Other Subjects
copper ion; nickel; nitric oxide; protein bax; protein bcl 2; s nitrosoglutathione; apoptosis; article; cancer cell culture; colon adenocarcinoma; colon carcinoma; DNA damage; human; human cell; polyacrylamide gel electrophoresis; priority journal; protein expression; spectrofluorometry; Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; bcl-Associated Death Protein; Carrier Proteins; Cations, Divalent; Colonic Neoplasms; Copper; Glutathione; HT29 Cells; Humans; Nickel; Nitric Oxide; Nitroso Compounds; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; S-Nitrosoglutathione; Spectrophotometry
Type
journal article