title: The role of apurinic/apyrimidinic endonuclease on the progression of streptozotocin-induced diabetic nephropathy in rats.
abstract: Apurinic/apyrimidinic endonuclease (APE) acts as a regulator of p53 or vice versa in the cellular response to oxidative stress. Since oxidative stress-induced apoptosis is suggested in the pathophysiology of diabetic nephropathy, we proposed that APE may have a feasible role in the progression of diabetic complications. We investigated the interrelationship between APE and p53 in streptozotocin-induced diabetic rat kidneys. Variable parameters on kidneys were checked 12 weeks after streptozotocin administration with or without chitosan oligosaccharide (COS) treatment. Streptozotocin administration caused changes as seen in early diabetic nephropathy with increased kidney size, increased p53, decreased APE, and increased cleaved caspase-3. COS was not suspected as being detrimental to renal measurements, and caused the augmentation of APE after streptozotocin administration. The augmented APE, in association with increased p53, suppressed cleaved caspase-3. 8-OHdG was mainly immunolocalized in the distal tubules, but also in the proximal tubules after streptozotocin administration without COS treatment, while APE was observed in proximal tubules in all groups. These results suggested that p53-dependent apoptosis resulting in suppressed APE might be an underlying mechanism of streptozotocin-induced nephropathy.
authors.affiliation: Department of Internal Medicine, Seoulpaik Hospital, Inje University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jin Nam
authors.initials: JN
authors.lastname: Kim
authors.forename: In Youb
authors.initials: IY
authors.lastname: Chang
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Kim
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Kyeong-Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Hyun Il
authors.initials: HI
authors.lastname: Kim
authors.forename: Sang Pil
authors.initials: SP
authors.lastname: Yoon
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D048271:Chitosan / Q000494:pharmacology / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004249:DNA Damage; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D020536:Enzyme Activators / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D020536:Enzyme Activators; D016159:Tumor Suppressor Protein p53; D013311:Streptozocin; D048271:Chitosan; D003404:Creatinine; C505410:Casp3 protein, rat; D053148:Caspase 3; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase