RESUMO
Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli.
Assuntos
Envelhecimento/metabolismo , Sulfeto de Hidrogênio/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Sulfetos/metabolismo , Animais , Caenorhabditis elegans , Linhagem Celular , Cicloexanonas/química , Cisteína/química , Cisteína/metabolismo , Drosophila melanogaster , Escherichia coli , Fibroblastos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Saccharomyces cerevisiae , Coloração e RotulagemRESUMO
BACKGROUND: To assess pelvic (P) and/or paraaortic (PA) lymph node (LN) involvement in patients with primary stage IA-IVA cervical cancer, (18)F-fluorodeoxyglucose (FDG)-PET, and MRI were compared with histological results. MATERIALS AND METHODS: Forty patients were prospectively evaluated. Twenty-eight patients underwent radio-chemotherapy (RT-CT) after initial staging and lymph node dissection (LND). RESULTS: PLN metastases were present in 6/31 patients. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) and accuracy in detecting PLN metastases were 67%, 84%, 50%, 91% and 81%, with MRI, and 33%, 92%, 50%, 85% and 81%, with FDG-PET. PALN metastases were present in 5/27 patients. Sensitivity, specificity, PPV, NPV and accuracy were 60%, 73%, 33%, 89% and 70% with MRI and 100%, 77%, 50%, 100% and 81% with FDG-PET in detecting PALN metastasis. CONCLUSION: FDG-PET is less accurate than MRI for PLN, but more accurate for PALN; FDG-PET cannot replace PA surgical procedures, but could guide them.