Cytotoxicity of nitric oxide is alleviated by zinc-mediated expression of antioxidant genes.

摘要: Metallothioneins (MTs) are small, cysteine-rich zinc binding proteins that powerful antioxidants. In this study, we investigated the interaction between zinc, MTs, and other components of antioxidant defense system in HepG2 cells. Cells were preincubated with then exposed to sodium nitroprusside (SNP), a nitric oxide (NO) donor. Both pretreatment SNP exposure separately induced transcription MT genes (MT1A, MT2A, MT1E, MT1X), as measured using real time-polymerase chain reaction (PCR) after reverse (RT). Pretreatment cells sulfate (ZnSO4) followed by caused glucose-6-phosphate dehydrogenase (G6PD) mRNA levels increase more than only SNP. However, when incubated N,N,N',N'-tetrakis(2-pyridylmethyl)ethyl-enediamine (TPEN), membrane-permeant Zn2+ chelator, stimulation was blocked, suggesting SNP-induced upregulation these is zinc-dependent. Human glutathione-S-transferase (hGSTA1) G6PD treated 5 microM TPEN decreased. Additionally, induction appears be mediated metal-activated factor-1 (MTF-1), which labile cytosol. cytotoxicity inhibited preincubation zinc. Taken together, results suggest NO plays an important role regulation cellular homeostasis NO-mediated release protein-bound may signal defense.