Regulation of the apoptosis‐related genes, Bax and Bcl‐2, in the early stage of diabetes mellitus

Abstract

SUMMARY: Apoptosis is related to a particular phase of the pathogenesis of diabetic nephropathy. the aim of the study is to investigate if (and if so where in the kidney) apoptotic changes occur during the early stage of diabetes mellitus. the incidence of renal cell apoptosis and its related Bcl‐2 proteins was investigated in the early stage of streptozotocin‐induced diabetic rats, using histological sections as well as isolated nephron segments and high glucose treatments in vitro. Modulation of the induced changes with the angiotensin‐converting enzyme (ACE) inhibitor, temocapril, was also analysed. Reverse transcription (RT)‐competitive polymerase chain reaction and western blot analysis were used. Glucose caused an increase of Bax mRNA expression in glomeruli and in the proximal straight tubule (PST), but not in the inner medullary collecting duct (IMCD). Glucose induced a decrease (40%) of Bcl‐2 mRNA expression in PST but not in glomeruli or in IMCD. Western blotting showed an increase of Bax protein expression in PCT, PST, and medullary thick ascending limb (MAL), and a decrease of Bcl‐2 protein expression in PST in diabetic rats. the ratio of Bcl‐2 to Bax decreased in PCT and PST in diabetic rats. the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labelling (TUNEL) method revealed the presence of apoptotic cells in proximal tubules in diabetic rats. Short‐term administration of temocapril did not affect Bax and Bcl‐2 protein expression in PCT or PST of diabetic rats. In conclusion, high ambient glucose could directly induce apoptotic changes in proximal tubules but not in glomeruli or in distal tubules at the early stage of diabetes mellitus.