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Int J Clin Exp Pathol ; 8(10): 12207-15, 2015.
Article in English | MEDLINE | ID: mdl-26722405

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.


Subject(s)
Apoptosis/drug effects , Benzamides/pharmacology , Poly (ADP-Ribose) Polymerase-1/drug effects , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Spinal Cord Injuries/drug therapy , Animals , Apoptosis Inducing Factor/drug effects , Apoptosis Inducing Factor/genetics , Apoptosis Inducing Factor/metabolism , Caspase 3/drug effects , Caspase 3/genetics , Caspase 3/metabolism , Disease Models, Animal , Humans , Injections, Spinal , Male , Oxidative Stress/drug effects , Poly (ADP-Ribose) Polymerase-1/genetics , Poly (ADP-Ribose) Polymerase-1/metabolism , Proto-Oncogene Proteins c-bcl-2/drug effects , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley
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