Transcriptional regulation of lactate dehydrogenase activity in rat kidney cells in diabetic nephropathy

Abstract

Aim. To study the features of transcriptional regulation of the activity and isoenzyme composition of lactate dehydrogenase in the kidneys of Rattus norvegicus L. in diabetic nephropathy.Materials and methods. The study included 20 male laboratory rats (Rattus norvegicus L.) divided into two equal groups: “Norm” – intact rats injected with 0.9% NaCl intraperitoneally and “Diabetes” – animals with alloxaninduced diabetes (DM1 model). The activity, subcellular localization, and mobility of lactate dehydrogenase (LDH, EC 1.1.1.27) isoenzymes were studied using spectrophotometry and electrophoresis. LDHA and LDHB gene transcripts were analyzed by the polymerase chain reaction.Results. Analysis of the LDH activity showed that this parameter increased by more than 6 times in the animals with diabetic nephropathy compared to the control group. Moreover, the increase in the rate of the LDH activity was a consequence of the enzyme activation in all the studied compartments of the cell and is consistent with the parameter in the homogenate. The increase in the LDH activity in diabetic nephropathy may result from redistribution of the activity rate between the available isoforms and may be associated with an increase in the transcription rate of genes encoding subunits A and B of this enzyme.Conclusion. The increase in the LDH activity is likely associated with the activation of renal gluconeogenesis, the main substrate for which is lactic acid reabsorbed in the renal glomeruli. The revealed increase in the LDH activity in the kidneys of rats with diabetic nephropathy may be associated with adaptation of their metabolism to the pathological state.