Cysteine S-nitrosation and S-sulfination are naturally occurring post-translational modifications (PTMs) on proteins induced by physiological signals and redox stress. Here we demonstrate that sulfinic acids and nitrosothiols react to form a stable thiosulfonate bond, and leverage this reactivity using sulfinate-linked probes to enrich and annotate hundreds of endogenous S-nitrosated proteins. In physiological buffers, sulfinic acids do not react with iodoacetamide or disulfides, enabling selective alkylation of free thiols and site-specific analysis of S-nitrosation. In parallel, S-nitrosothiol-linked probes enable enrichment and detection of endogenous S-sulfinated proteins, confirming that a single sulfinic acid can react with a nitrosothiol to form a thiosulfonate linkage. Using this approach, we find that hydrogen peroxide addition increases S-sulfination of human DJ-1 (PARK7) at Cys106, whereas Cys46 and Cys53 are fully oxidized to sulfonic acids. Comparative gel-based analysis of different mouse tissues reveals distinct profiles for both S-nitrosation and S-sulfination. Quantitative proteomic analysis demonstrates that both S-nitrosation and S-sulfination are widespread, yet exhibit enhanced occupancy on select proteins, including thioredoxin, peroxiredoxins, and other validated redox active proteins. Overall, we present a direct, bidirectional method to profile select redox cysteine modifications based on the unique nucleophilicity of sulfinic acids.
Functionalized fullerenes represent a new class of photosensitizer (PS) that is being investigated for photodynamic therapy (PDT) of various diseases including cancer. We tested the hypothesis that fullerenes could be used to mediate PDT of intraperitoneal (IP) carcinomatosis in a mouse model. In humans this form of cancer responds poorly to standard treatment and manifests as a thin covering of tumor nodules on intestines, and other abdominal organs. We used a colon adenocarcinoma cell line (CT26) stably expressing luciferase to allow monitoring of IP tumor burden in BALB/c mice by non-invasive real-time optical imaging using a sensitive low light camera. IP injection of a preparation of N-methylpyrrolidinium-fullerene formulated in Cremophor-EL micelles, followed by white-light illumination delivered through the peritoneal wall (after creation of a skin flap) produced a statistically significant reduction in bioluminescence and a survival advantage in mice.
Background:The functions of palmitate turnover in signal transduction are poorly understood. Results: Inhibiting palmitate turnover on R7BP redistributed R7BP-R7 RGS complexes from the plasma membrane to endomembranes, dissociated them from GIRK channels, and delayed G i/o deactivation and channel closure. Conclusion: Palmitate turnover on R7BP promotes GIRK channel deactivation. Significance: Inhibiting palmitate turnover on R7BP could enhance GIRK activity in neurological disorders.
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