Rabbit Anti-Human Thioredoxin 1 monoclonal antibody, clone I.864.9

This present study aims to verify the underlying mechanism that anti-aging protein Klotho protects cartilages against the damage induced by oxidative stress. The Klotho expression level in the articular cartilages of mice with osteoarthritis (OA) was measured by using western blotting and quantitative real-time PCR. This work also investigated the effects of Klotho on chondrocyte functions, such as PI3K/Akt pathway, apoptosis and reactive oxygen species (ROS) production, through overexpressing Klotho in chondrocytes by transfecting with the plasmid encoding Klotho. The results showed that Klotho expression level obviously decreased in the articular cartilages of OA mice. It was also found that mechanical loading significantly reduced the expression and activity of Klotho in chondrocytes. In addition, the overexpression of Klotho suppressed chondrocyte apoptosis through thioredoxin/peroxiredoxin (Trx/Prx) family and ROS/TXNIP/NLRP3 signaling pathways. All these above findings suggest that Klotho is essential in OA progression, and may be a good target for the research and development of the drugs for OA treatment.

Diabetes is characterized by hyperglycemia, loss of functional islet beta cell mass, deficiency of glucose-lowering insulin, and persistent alpha cell secretion of gluconeogenic glucagon. Still, no therapies that target these underlying processes are available. We therefore performed high-throughput screening of 300,000 compounds and extensive medicinal chemistry optimization and here report the discovery of SRI-37330, an orally bioavailable, non-toxic small molecule, which effectively rescued mice from streptozotocin- and obesity-induced (db/db) diabetes. Interestingly, in rat cells and in mouse and human islets, SRI-37330 inhibited expression and signaling of thioredoxin-interacting protein, which we have previously found to be elevated in diabetes and to have detrimental effects on islet function. In addition, SRI-37330 treatment inhibited glucagon secretion and function, reduced hepatic glucose production, and reversed hepatic steatosis. Thus, these studies describe a newly designed chemical compound that, compared to currently available therapies, may provide a distinct and effective approach to treating diabetes.