RESUMEN
Sharply rising oxidative stress and ineffectual angiogenesis have imposed restrictions on diabetic wound healing. Here, a photothermal-responsive nanodelivery platform (HHC) was prepared by peroxidase (CAT)-loaded hollow copper sulfide dispersed in photocurable methacrylamide hyaluronan. The HHC could scavenge reactive oxygen species (ROS) and promote angiogenesis by photothermally driven CAT and Cu2+ release. Under near-infrared light irradiation, the HHC presented safe photothermal performance (<43 °C), efficient bacteriostatic ability against E. coli and S. aureus. It could rapidly release CAT into the external environment for decomposing H2O2 and oxygen generation to alleviate oxidative stress while promoting fibroblast migration and VEGF protein expression of endothelial cells by reducing intracellular ROS levels. The nanodelivery platform presented satisfactory therapeutic effects on murine diabetic wound healing by modulating tissue inflammation, promoting collagen deposition and increasing vascularization in the neodermis. This HHC provided a viable strategy for diabetic wound dressing design.
Asunto(s)
Cobre , Diabetes Mellitus , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Cobre/uso terapéutico , Células Endoteliales/metabolismo , Staphylococcus aureus/metabolismo , Escherichia coli/metabolismo , Angiogénesis , Peróxido de Hidrógeno , Sulfuros/farmacología , Antibacterianos/uso terapéutico , HidrogelesRESUMEN
Oxidative damage caused by the accumulation of reactive oxygen species (ROS) is one of the main obstacles to the improvement of microbial cell growth and fermentation characteristics under adverse environments. And the antioxidant capacity of cells will increase with the cell growth. Here, we found that a transition state transcription factor AbrB related to changes in cell growth status could regulate the accumulation of ROS and antioxidant capacity in Bacillus licheniformis. The results showed that the accumulation of intracellular ROS was reduced by 23.91â¯% and the cell survival rates were increased by 1.77-fold under 0.5â¯mM H2O2 when AbrB was knocked out. We further mapped regulatory target genes of AbrB related to ROS generation or clearance based on our previously analyzed transcriptome sequencing. It proved that AbrB could promote ROS generation via upregulating the synthesis of oxidase and siderophores, and negatively regulating the synthesis of iron chelators (pulcherriminic acid, and H2S). Additionally, AbrB could inhibit ROS clearance by negatively regulating the synthesis of antioxidase (superoxide dismutase, catalase, peroxidase, thioredoxin, thioredoxin reductase) and cysteine. Those results illustrated that the inactivation of AbrB during the stationary phase, along with its control over ROS generation and clearance, might represent a vital self-protection mechanism during cell evolution. Overall, the systematic investigation of the multi-pathway regulation network of ROS generation and clearance highlights the important function of AbrB in maintaining intracellular redox balance.
Asunto(s)
Antioxidantes , Bacillus licheniformis , Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno , Factores de Transcripción , Especies Reactivas de Oxígeno/metabolismo , Bacillus licheniformis/metabolismo , Bacillus licheniformis/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Peróxido de Hidrógeno/metabolismo , Antioxidantes/metabolismo , Estrés Oxidativo , Sideróforos/metabolismoRESUMEN
The oyster Crassostrea hongkongensis is an ideal biomonitor due to its widespread distribution along the coast of Southern China and the ability to hyperaccumulate metals including Cu and Zn. In this study, we conducted the first investigation of the molecular responses to metal hyperaccumulation based on quantitative shotgun proteomics technique and genome information. Gill tissue of oysters collected from the uncontaminated environment (Site 1, 59.6 µg/g and 670 µg/g dry weight for Cu and Zn) displayed significant protein profile differentiation compared to those from a moderately contaminated (Site 2, 1,465 µg/g and 10,170 µg/g for Cu and Zn) and a severely contaminated environment (Site 3, 3,899 µg/g and 39,170 µg/g for Cu and Zn). There were 626 proteins identified to be differentially expressed at Site 3 but only 247 proteins at Site 2. Oysters from a moderately contaminated estuary (Site 2) displayed fewer effects as compared to oysters under severe contamination, with fluctuated small molecule metabolism and enhanced translation process. At Site 3, the induction of reactive oxygen species (ROS) was the main toxicity under the extremely high level of metal stress, which resulted in protein damage. Additionally, the impaired structure of cytoskeleton and modified membrane tracking process at Site 3 oysters led to the blockage or less efficient protein or macromolecule distribution within cells. Nonetheless, proteomic analysis in this study revealed that oysters could partly alleviate the adverse metal effects by boosting the translation process, enhancing the ability to recycle the misfolded proteins, and enhancing the potential to eliminate the excess ROS. Our study demonstrated an adaptive potential of oysters at the protein level to survive under conditions of metal hyper-accumulation.