Endocrine Imbalance Associated With Proteome Changes in Diabetes

The dynamics of cellular metabolism involves rapid interactions between proteins and nucleic acids, proteins and proteins, and signaling. These involve the interactions with respect to the sulfur bond, noncovalent electrostatic interactions, protein structure stabilization and protein-ligand binding, weak electrostatic interactions in proteins, oxygen radicals that initiate a change in conformation and a chain of events. We review a development in molecular medicine that is a very promising work in progress. We also review the current and future research methods involving mitochondria. Long-term effects of diabetes include glycation of proteins, for example, glycohemoglobin (HbA1c), increased risk of cardiovascular diseases, atherosclerosis, retinopathy, nephropathy, and neurological dysfunctions. Tissues are exposed to significant quantities of highly reactive chemical species including nitric oxide ^• NO and reactive oxygen species ROS over months to years, to an extent generated by mitochondrial activities. The reactions of ^• NO can be broadly discussed with reference to three main processes which control their fate in biological systems: (1) diffusion and intra-cellular consumption; (2) autooxidation to form nitrous anhydride N₂ O₃ ; and (3) reaction with superoxide O2^• - to form peroxynitrite ONOO-. Reactive nitrogen species produced by macrophages and neutrophils in the interstitial space, with emphasis on ^• NO, N₂ O₃ , ONOO-, and nitrogen dioxide radicals ^• NO₂ generate protein and DNA damage. Serum thiol (-SH) groups act as an important extracellular scavenger of peroxides and are therefore helpful in protecting the surrounding tissues. The events described here are a homeostatic endocrine imbalance that is associated with proteostasis. The advances we have seen in untangling this web of interactions are sure to continue at a breathtaking pace. J. Cell. Biochem. 118: 3569-3576, 2017. © 2017 Wiley Periodicals, Inc.