title: 3-aminobenzamide, one of poly(ADP-ribose)polymerase-1 inhibitors, rescuesapoptosisin rat models of spinal cord injury.
abstract: Poly(ADP-ribose)polymerase-1 (PARP-1) is anubiquitous, DNA repair-associated enzyme, which participates in gene expression, cell death, central nerve system (CNS) disorders and oxidative stress. According to the previous studies, PARP-1 over-activation may lead to over-consumption of ATP and even cell apoptosis. Spinal cord injury (SCI) is an inducement towards PARP-1 over-activation due to its massive damage to DNA. 3-aminobenzamide (3-AB) is a kind of PARP-1 inhibitors. The relationship among PARP-1, 3-AB, SCI and apoptosis has not been fully understood. Hence, in the present study, we focused on the effects of 3-AB on cell apoptosis after SCI. Accordingly, SCI model was constructed artificially, and 3-AB was injected intrathecally into the Sprague-Dawley (SD) rats. The results demonstrated an increase in cell apoptosis after SCI. Furthermore, PARP-1 was over-activated after SCI but inhibited by 3-AB injection. In addition, apoptosis-inducing factor (AIF) was inhibited but B-cell lymphoma-2 (Bcl-2) was up-regulated by 3-AB. Interestingly, caspase-3 was not significantly altered with or without 3-AB. In conclusion, our experiments showed that 3-AB, as a PARP-1 inhibitor, could inhibit cell apoptosis after SCI in caspase-independent way, which could provide a better therapeutic target for the treatment of SCI.
authors.affiliation: Department of Orthopaedics, Zoucheng People's Hospital Zoucheng 273500, Shandong, China.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Orthopaedics, Shanghai No.6 People's Hospital Shanghai 200025, China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Orthopaedics, Zoucheng People's Hospital Zoucheng 273500, Shandong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of Orthopaedics, Zoucheng People's Hospital Zoucheng 273500, Shandong, China.
authors.forename: Ziling
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Jining Medical College Jining 272001, Shandong, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C025160:3-aminobenzamide; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D053148:Caspase 3
keywords: 3-AB; PARP-1; SCI; apoptosis; inhibitors