Effects of advanced glycation end product modification on proximal tubule epithelial cell processing of albumin.

Aim: The goal of this work is to understand the cellular effects of advanced glycation end product (AGE)-modified protein on renal proximal tubule cells.

Background: A major function of the proximal tubule is to reabsorb and process filtered proteins. Diabetes is characterized by increased quantities of tissue and circulating proteins modified by AGEs.

Processing advanced glycation end product-modified albumin by the renal proximal tubule and the early pathogenesis of diabetic nephropathy.

Diabetes is characterized by increased quantities of circulating proteins modified by advanced glycation end products (AGEs). Proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs. The proximal tubule binds, takes up, and catabolizes AGE-modified albumin by pathways different from those of unmodified albumin.

Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation.

Chronic hyperglycemia causes structural alterations of proteins through the Maillard reaction. In diabetes, methylglyoxal (MGO)-induced hydroimidazolones are the predominant modification. In contrast to acute hyperglycemia, mitochondrial respiration is depressed in chronic diabetes.

Inositol hexakisphosphate kinase 2 sensitizes ovarian carcinoma cells to multiple cancer therapeutics.

We recently identified inositol hexakisphosphate kinase 2 (IP6K2) as a positive regulator of apoptosis. Overexpression of IP6K2 enhances apoptosis induced by interferon-beta (IFN-beta) and cytotoxic agents in NIH-OVCAR-3 ovarian carcinoma cells. In this study, we contrast and compare IFN-beta and radiation-induced death, and show that IP6K2 expression sensitizes tumor cells.