title: Immunohistochemical Aspects of Cell Death in Diabetic Nephropathy.
abstract: BACKGROUND
  Diabetes Mellitus causes ultrastructural changes triggered by partially clarified cellular mechanisms. Since cell death is an important mechanism in the appearance and progression of diabetic nephropathy, we studied alteration of several markers of apoptotic pathways signaling in renal tissue of diabetic or prediabetic patients.
  
  
  METHODS
  We analyzed 48 human kidney tissue samples divided into two study groups: the research group (43 renal tissue samples from diabetic or prediabetic patients), and the control group (5 renal tissue samples from patients without diabetes). Immunohistochemistry revealed expression of Bcl-2, APAF-1, CD-95 and Caspase-9 in the renal cortical structures. Statistical analysis was also performed (significance level P < 0.05).
  
  
  RESULTS
  We found a variable expression of the antiapoptotic Bcl-2 with a decrease of Bcl-2 expression in diabetes. The control samples render evident intensely positive immunostaining for CD-95. In diabetes and diabetic nephropathy, there was positive immunostaining for APAF-1 at tubular cell level. Nuclear and cytoplasmic positivity for Caspase-9 was more frequently recorded as kidney damage progresses. APAF-1 and Caspase-9 positivity are arguments for an intrinsic apoptotic mechanism of cell death in diabetic nephropathy.
  
  
  CONCLUSIONS
  The mechanisms of apoptotic cell death identified in diabetic kidney samples prove that Bcl-2, CD-95, APAF-1 and Caspase-9 represent reliable markers of cell death in human renal tissue. Our results support the hypothesis that apoptosis is a pathogenic and initiator mechanism of renal remodeling in diabetic kidney disease.
authors.forename: Elena
authors.initials: E
authors.lastname: Bălăşescu
authors.forename: Mirela
authors.initials: M
authors.lastname: Cioplea
authors.forename: Alice
authors.initials: A
authors.lastname: Brînzea
authors.forename: Roxana
authors.initials: R
authors.lastname: Nedelcu
authors.forename: Sabina
authors.initials: S
authors.lastname: Zurac
authors.forename: Daniela Adriana
authors.initials: DA
authors.lastname: Ion
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism*; D016022:Case-Control Studies; D053453:Caspase 9 / Q000378:metabolism*; D016923:Cell Death; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; C000595707:BCL2 protein, human; C491901:FAS protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; C506433:CASP9 protein, human; D053453:Caspase 9