title: Tempol reduces podocyte apoptosis via PARP signaling pathway in experimental diabetes mellitus.
abstract: OBJECTIVE
  In diabetic hypertensive rats, tempol reduces albuminuria by restoring the redox imbalance. Increased formation of reactive oxygen species leading to activation of poly(ADP-ribose) polymerase (PARP)-1 and podocyte loss by apoptosis contribute to albuminuria in diabetes mellitus (DM). In the present study, we investigated the hypothesis that in DM tempol reduces albuminuria by inhibition of PARP-induced podocyte apoptosis.
  
  
  METHODS
  DM was induced in 4-week-old spontaneously hypertensive rats by streptozotocin. Mouse and human podocyte cell lines were cultured in normal or high-glucose conditions, with or without tempol and/or a PARP-1 inhibitor, PJ34.
  
  
  RESULTS
  In diabetic rats, tempol treatment did not affect plasma glucose levels or systolic blood pressure. Albuminuria was higher in diabetic rats, and it was reduced by tempol. DM leads to an elevation of glomerular apoptotic cells and to podocyte loss; both were prevented by tempol treatment. DM increases the expression of poly(ADP-ribose)-modified proteins in isolated glomeruli, and it was reduced by tempol. In vitro, high glucose increased caspase-3 activity and led to a higher number of apoptotic cells that were prevented by tempol and the PARP-1 inhibitor.
  
  
  CONCLUSIONS
  In DM, tempol reduces albuminuria associated with reduction of podocyte apoptosis and decreasing oxidative stress via PARP signaling.
authors.affiliation: Renal Pathophysiology Laboratory, Investigation on Diabetes Complications, Division of Nephrology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
authors.forename: Elisa B M I
authors.initials: EB
authors.lastname: Peixoto
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lopes de Faria
authors.forename: Jose B
authors.initials: JB
authors.lastname: Lopes de Faria
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000517:prevention & control / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002461:Cell Line, Transformed; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000652:urine; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D015398:Signal Transduction / Q000187:drug effects*; D013113:Spin Labels; D013311:Streptozocin
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D008565:Membrane Proteins; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013113:Spin Labels; C113267:nephrin; D013311:Streptozocin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; C001803:tempol