title: Apurinic/apyrimidinic endonuclease 1 on aging-associated deteriorations in rat kidneys.
abstract: We have reported a possible involvement of apurinic/apyrimidinic endonuclease 1 (APE1), one of the DNA repair pathways, in various nephropathy models and found that there is a close connection between APE1 and p53-dependent apoptosis. Therefore, we investigated the changes of APE in aging rat kidney since aging is the consequence of increased susceptibility to apoptosis and impaired repair. Characteristics of chronological aging were compared among 6-, 24- and 28-month-old male Sprague-Dawley rats. Serum blood urea nitrogen and creatinine were measured for renal function. Western blot assay was compared for p53, bax, cleaved caspase 3, rH2AX, and APE1. Immunohistochemical staining of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and APE1 was performed. Cellular senescence was checked by beta-galactosidase staining. Compared with young rats, aged rats showed significant increase in creatinine level with cellular senescence in the proximal convoluted tubules confirmed by beta-galactosidase staining. All the checked variables were significantly increased with aging: 1) increased p53, bax, and caspase 3 may activate the apoptotic pathway, 2) increased rH2AX and 8-OHdG immunolocalization in the proximal convoluted tubules might mean augmented DNA damage, and 3) increased APE1 might be caused by the immunoreactivity in the distal convoluted tubules while decreased in the proximal convoluted tubules. These results suggested that APE1 might have little protective effects on p53-dependent apoptosis irrespective of DNA repair activities in aged renal proximal tubules. Therefore, researchers should use older animals than 24-month-old rats in future studies for investigating the relationship between the apoptosis and DNA repair in the aging kidneys.
authors.affiliation: Department of Anatomy, College of Medicine, Chosun University , Gwangju , Republic of Korea.
authors.forename: In Youb
authors.initials: IY
authors.lastname: Chang
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Jin Nam
authors.initials: JN
authors.lastname: Kim
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Sang Pil
authors.initials: SP
authors.lastname: Yoon
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004249:DNA Damage; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology* / Q000502:physiology; D007674:Kidney Diseases / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D001616:beta-Galactosidase / Q000097:blood
chemical_list: D003404:Creatinine; D001616:beta-Galactosidase; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: APE1; aging; apoptosis; renal proximal tubule