Tyrosine nitration of glucagon impairs its function: Extending the role of heme in T2D pathogenesis.

New studies raise the possibility that the higher glucagon (GCG) level present in type 2 diabetes (T2D) is a compensatory mechanism to enhance ß-cell function, rather than induce dysregulated glucose homeostasis, due to an important role for GCG that acts directly within the pancreas on insulin secretion by intra-islet GCG signaling. However, in states of poorly controlled T2D, pancreatic α cell mass increases (overproduced GCG) in response to insufficient insulin secretion, indicating decreased local GCG activity. The reason for this decrease is not clear. Recent evidence has uncovered a new role of heme in cellular signal transduction, and its mechanism involves reversible binding of heme to proteins. Considering that protein tyrosine nitration in diabetic islets increases and glucose-stimulated insulin secretion (GSIS) decreases, we speculated that heme modulates GSIS by transient interaction with GCG and catalyzing its tyrosine nitration, and the tyrosine nitration may impair GCG activity, leading to loss of intra-islet GCG signaling and markedly impaired insulin secretion. Data presented here elucidate a novel role for heme in disrupting local GCG signaling in diabetes. Heme bound to GCG and induced GCG tyrosine nitration. Two tyrosine residues in GCG were both sensitive to the nitrating species. Further, GCG was also demonstrated to be a preferred target peptide for tyrosine nitration by co-incubation with BSA. Tyrosine nitration impaired GCG stimulated cAMP-dependent signaling in islet ß cells and decreased insulin release. Our results provided a new role of heme for impaired GSIS in the pathological process of diabetes.

Mussel inspired multifunctional bovine serum albumin (BSA) coatings loaded with Baicalein (BAI) to enhance osteogenesis and resist oxidative stress for potential application on implant.

Oxidative stress is associated with most traumatic or pathological bone defects, and seriously affects the effect of implantation. The construction of antioxidative and osteogenic coatings is of great significance to accelerate the bone regeneration of implants. In this study, baicalein (BAI), a nature flavonoid drug, was loaded in bovine serum albumin (BSA) by desolvent method to prepare BAI-BSA composite protein, and tannic acid (TA)/BAI-BSA coatings were further built via layer by layer self-assembly technology. BAI-BSA possesses good biocompatibility that showed no cytotoxicity to osteoblasts and erythrocytes, and helps to enhance the activity of alkaline phosphatase (ALP) and promote the formation of osteogenic mineralized calcium nodules. After assembled with TA, BAI-BSA coating significantly promoted cell adhesion and in vitro osteogenic mineralization of MC3T3-E1. Moreover, BAI drug loading improved the antioxidative function of BSA coatings effectively. The scavenging rates of (TA/BAI-BSA-10)4 for ABTS+• and DPPH• free radicals were 69.6 ± 16.1 % and 53.4 ± 2.4 %, respectively. At cellular level, the TA/BAI-BSA coating effectively inhibited the impact of oxidative stress on the oxidative damage of osteoblasts. The drug-loaded protein coatings possess both great antioxidative and osteogenic functions, which have important potential in the field of bone repair.

The Preparation and Effects of Organic-Inorganic Antioxidative Biomaterials for Bone Repair.

Reactive oxygen species (ROS) has great influence in many physiological or pathological processes in organisms. In the site of bone defects, the overproduced ROS significantly affects the dynamic balance process of bone regeneration. Many antioxidative organic and inorganic antioxidants showed good osteogenic ability, which has been widely used for bone repair. It is of great significance to summarize the antioxidative bone repair materials (ABRMs) to provide guidance for the future design and preparation of osteogenic materials with antioxidative function. Here, this review introduced the major research direction of ABRM at present in nanoscale, 2-dimensional coating, and 3-dimensional scaffolds. Moreover, the referring main active substances and antioxidative properties were classified, and the positive roles of antioxidative materials for bone repair have also been clearly summarized in signaling pathways, antioxidant enzymes, cellular responses and animal levels.