Аpoptosis-dependent damages in children with diabetic nephropathy

Abstract

Diabetic nephropathy is the leading cause of death in patients with diabetes mellitus type I (T1D). Formation of diabetic nephropathy depends on the quality of blood glucose level control an indicator of which is a level of glycosylated hemoglobin (HbA1c). The aim of the study was to investigate the level of metabolic-hypoxic disorders and the condition of apoptosis controlling system in diabetic nephropathy children. The study involved 34 children with type I diabetes and diabetic nephropathy (aged 6 to 17 years). The affinity of hemoglobin to oxygen determined by spectrophotometric method. The levels of the marker of cellular hypoxia HIF-1alfa, levels of the apoptotic factor caspase-3 have been studied by Western Blotting. In the group of children with newly diagnosed T1D an increased rate of dissociation of oxygen and hemoglobin compared to the control group was detected. Children with DN the levels of this index were significantly lower than the control group. We show stage-dependent manner in increase of the cellular hypoxia and apoptotic effector caspase-3 levels. Both markers were detected at significantly higher rate in DN patients as compared to T1D. Thus, the development of DN in children is associated with violation of Hb/oxygen dissociation, a sign of the high degree of the Hb glycosylation resulting to the formation of cellular hypoxia and activation of apoptosis, as one of the basic mechanisms of cell damage kidneys in DN.