RESUMO
Glutathione (GSH), an abundant non-protein thiol, plays a crucial role in numerous biotic processes. Herein, a mitochondria-targeted near-infrared GSH probe (JGP) was synthesized, which displayed desired properties with high specificity and sensitivity, appreciable water solubility, and rapid response time. In the presence of GSH, nearly a 13-fold fluorescence emission growth appeared at 730 nm and the solvent color changed from blue to cyan. The sensing mechanism of JGP and GSH was confirmed by a high-resolution mass spectroscopy analysis. Moreover, good cell penetration enabled JGP to be successfully used for imaging biological samples such as HeLa cells, C. elegans, and especially rat brain slices. Imaging experiments showed that JGP could monitor the GSH concentration changes with a dose-dependent direct ratio in all the tested samples. The successful application of JGP in brain imaging indicates that JGP is a suitable GSH optical probe, which may have wide application value in fields of brain imaging. It also lays a theoretical and practical foundation for the further application of fluorescent probes in brain sciences.
RESUMO
We reported for the first time that cationic pillar[6]arene (cPA6) could tightly bind to peptide polymer (MW~20-50 kDa), an artificial substrate for tyrosine (Tyr) phosphorylation, and efficiently inhibit Tyr protein phosphorylation through host-guest recognition. We synthesized a nanocomposite of black phosphorus nanosheets loaded with cPA6 (BPNS@cPA6) to explore the effect of cPA6 on cells. BPNS@cPA6 was able to enter HepG2 cells, induced apoptosis, and inhibited cell proliferation by reducing the level of Tyr phosphorylation. Furthermore, BPNS@cPA6 showed a stronger ability of inhibiting cell proliferation in tumor cells than in normal cells. Our results revealed the supramolecular modulation of enzymatic Tyr phosphorylation by the host-guest recognition of cPA6.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Antineoplásicos/administração & dosagem , Cátions/administração & dosagem , Cátions/farmacologia , Portadores de Fármacos/química , Células Hep G2 , Humanos , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fósforo/química , Compostos de Amônio Quaternário/administração & dosagem , Tirosina/metabolismoRESUMO
The redox-regulator glutathione (GSH) maintains a specific redox potential to sustain routine cellular activity from oxidative damage. In the early stage of the cell cycle process, the glutathione levels increase in the nuclei for protecting the DNA replication process from reactive oxygen species (ROS). In the first attempt, we developed a new ratiometric fluorescent probe that has provided information about glutathione levels in the nuclei. The UV-vis. absorption of probe GScp has shown a hypsochromic shift from 410 to 350 nm in the presence of GSH. In fluorescence titration, we observed that fluorescence emission of the GScp switched from 510 to 460 nm in the presence of GSH. The self-calibrated probe GScp has shown nearly optimal reversibility in GSH redox dynamics with the dissociation constant 2.47 mM. The probe is ideal for GSH tracking in live cells, as its toxicity has within the safe zone. The probe GScp has validated GSH levels in nucleoli by providing fluorescence images in blue-channel. This finding inspires us to use for validation of GSH dynamics in the nucleoli in the cell cycle process.