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S-nitrosylation of the Peroxiredoxin-2 promotes S-nitrosoglutathione-mediated lung cancer cells apoptosis via AMPK-SIRT1 pathway.

ABSTRACT: Protein S-nitrosylation, the redox-based posttranslational modification of a cysteine thiol by the attachment of a nitric oxide (NO) group, is responsible for a variety of signaling effects. Dysregulation of S-nitrosylation may be directly linked to cancer apoptotic resistance and cancer therapy outcomes, emphasizing the importance of S-nitrosylation in cancer. Peroxiredoxin-2 (Prdx2), an antioxidant enzyme, plays an important role in the protection of cancer cells from oxidative radical damage caused by hydrogen dioxide (H2O2), which is a potential target for cancer therapy. Our studies showed that, as an endogenous NO carrier, S-nitrosoglutathione (GSNO) induced apoptosis in lung cancer cells via nitrosylating Prdx2. The nitrosylation of Prdx2 at Cys51 and Cys172 sites disrupted the formation of Prdx2 dimer and repressed the Prdx2 antioxidant activity, causing the accumulation of endogenous H2O2. H2O2 activated AMPK, which then phosphorylated SIRT1 and inhibited its deacetylation activity toward p53 in A549 cells or FOXO1 in NCI-H1299 cells. Taken together, our results elucidate the roles and mechanisms of Prdx2 S-nitrosylation at Cys51 and Cys172 sites in lung cancer cells apoptosis and this finding provides an effective lung cancer treatment strategy for managing aberrant Prdx2 activity in lung cancers.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6465399 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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S-nitrosylation of the Peroxiredoxin-2 promotes S-nitrosoglutathione-mediated lung cancer cells apoptosis via AMPK-SIRT1 pathway.

Zhang Yihan Y Sun Changning C Xiao Guokai G Shan Hui H Tang Luyao L Yi Yujiao Y Yu Wengong W Gu Yuchao Y

Cell death & disease 20190415 5

Protein S-nitrosylation, the redox-based posttranslational modification of a cysteine thiol by the attachment of a nitric oxide (NO) group, is responsible for a variety of signaling effects. Dysregulation of S-nitrosylation may be directly linked to cancer apoptotic resistance and cancer therapy outcomes, emphasizing the importance of S-nitrosylation in cancer. Peroxiredoxin-2 (Prdx2), an antioxidant enzyme, plays an important role in the protection of cancer cells from oxidative radical damage ...[more]

PMID: 30988280

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Dataset Information

S-nitrosylation of the Peroxiredoxin-2 promotes S-nitrosoglutathione-mediated lung cancer cells apoptosis via AMPK-SIRT1 pathway.

Publications

S-nitrosylation of the Peroxiredoxin-2 promotes S-nitrosoglutathione-mediated lung cancer cells apoptosis via AMPK-SIRT1 pathway.

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