title: PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying.
abstract: It has been demonstrated that increases in poly(ADP-ribose) polymerase (PARP) activity causes damage to several organs under ischemia/reperfusion (I/R) conditions. The aims of this study were to investigate whether inhibition of PARP could suppress apoptosis in the bladder following acute urinary retention (AUR) and subsequent bladder emptying. Twelve-week-old male Sprague Dawley rats were divided into a control group, saline treated group, and 3-aminobenzamide (3-AB, a specific PARP inhibitor)-treated group. Sixty minutes after the administration of saline and 3-AB, the saline and 3-AB-treated groups had 60 min of over-distension and followed by 2 h of drainage. The degree of bladder apoptosis, levels of malondialdehyde (MDA), ATP and nicotinamide adenine dinucleotide (NAD+); expression of poly(ADP-ribose) (PAR), phosphorylation of protein kinase B (Akt); and levels of Bcl-2, Bax, and caspase 3 activity in the bladder were determined. Molecular and histological analyses showed that bladder apoptosis was associated with increases in the amount of PAR and decreases in ATP and NAD+ levels in the saline treated group. In addition, phosphorylated Akt and Bcl-2/Bax ratio were significantly decreased. The activity of caspase 3 was significantly increased in the saline treated group. Inhibition of PARP significantly increased the levels of ATP and NAD+, phosphorylation of Akt, and Bcl-2/Bax ratio, and significantly reduced the activation of caspase 3. As a result, apoptosis in the bladder was attenuated. These results indicate that PARP activation may be involved in apoptosis in the bladder induced by AUR and subsequent emptying via energy depletion and suppression of Akt activity.
authors.affiliation: Department of Urology and Andrology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200011, China. wenjili@naver.com
authors.forename: Wen Ji
authors.initials: WJ
authors.lastname: Li
authors.forename: Seung-June
authors.initials: SJ
authors.lastname: Oh
mesh_terms: D000818:Animals; D017209:Apoptosis; D015536:Down-Regulation; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000166:cytology / Q000293:injuries / Q000378:metabolism*; D016055:Urinary Retention / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases