A biomimetic was designed for the construction of a new efficient peroxidase-like nano artificial enzyme with a heme-imidazole component complexed with gemini 12-2-12/SDS supramolecules. The presence of a simple surfactant mixture (SDS/gemini 12-2-12 at a particular concentration) provided an apoprotein-like hydrophobic pocket for the heme-imidazole moiety, which produced a peroxidase active site containing positive and negative charges distributed on the colloidal surface. Vesicular structures that stabilized the heme-imidazole complexes formed multienzyme advanced colloids. The enzymatic activation parameters indicated that the catalytic efficiency of the novel nano artificial enzyme was 27% as efficient as the native horseradish peroxidase (HRP). The imidazole moiety, which functionally corresponded to the histidine ligand in the native HRP, increased the reactivity and catalytic efficiency of the artificial enzyme. The nano biocatalyst did not exhibit suicide inactivation until high concentrations of hydrogen peroxide, indicating that the vesicle hydrophobic pocket effectively shielded the active site, thereby controlling the concentration of hydrogen peroxide at the heme moiety and enabling high rates of enzymatic turnover.
The interactions between bilirubin and human serum albumin (HSA) were studied by isothermal titration calorimetry (ITC) and UV-vis spectrophotometry at 27 degrees C in 100 mM phosphate buffer pH 7.4 containing 1 mM EDTA. The biphasic shape of the HSA-bilirubin binding curve depicted the existence of two bilirubin binding sets on the HSA structure which had distinct binding interactions. Each binding set contained one or more bilirubin binding site. The first binding set at subdomain IIA included one binding site and had a more hydrophobic microenvironment than the other two binding sites in the second bilirubin binding set (subdomain IIIA). With our method of analysis, the calculated dissociation constant of the first binding site is 1.28 x 10(-6) M and 4.80 x 10(-4) M for the second and third binding sites. Here, the typical Boltzmann's equation was used with a new approach to calculate the dissociation constants as well as the standard free energy changes for the HSA-bilirubin interactions. Interestingly, our calculations obtained using the Wyman binding potential theory confirmed that our analysis method had been correct (especially for the second binding phase). The molar extinction coefficient determined for the first bound bilirubin molecule depicted that the bilirubin molecules (in low concentrations) should interact with the nonpolar microenvironment of the first high affinity binding site. Binding of the bilirubin molecules to the first binding site was endothermic (deltaH > 0) and occurred through the large increase in the binding entropy established when the hydrophobic bilirubin molecules escaped from their surrounding polar water molecules and into the hydrophobic medium of the first binding site. On the other hand, the calculated molar extinction coefficient illustrated that the microenvironment of the second binding set (especially for the third binding site) was less hydrophobic than the first one but still more hydrophobic than the buffer medium. The binding of the third bilirubin molecule to the HSA molecule was established more through exothermic (electrostatic) interactions.
Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells’ redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin.
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