RGD Reference Report - Diabetic cystopathy is associated with PARP/JNK/mitochondrial apoptotic pathway-mediated bladder apoptosis. - Rat Genome Database

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Diabetic cystopathy is associated with PARP/JNK/mitochondrial apoptotic pathway-mediated bladder apoptosis.

Authors: Li, WJ  Oh, SJ 
Citation: Li WJ and Oh SJ, Neurourol Urodyn. 2010 Sep;29(7):1332-7. doi: 10.1002/nau.20869.
RGD ID: 10053565
Pubmed: (View Article at PubMed) PMID:20879002
DOI: Full-text: DOI:10.1002/nau.20869

AIMS: Diabetic cystopathy, a common complication of diabetes, is frequently associated with an increase in oxidative stress and apoptosis of the bladder. Poly(ADP-ribose) polymerase (PARP) is activated under such conditions of oxidative stress, and plays a critical role in cell apoptosis. The aim of this study was to investigate whether the activation of PARP and subsequent activation of c-Jun N-terminal kinase (JNK) and the mitochondrial apoptotic pathway are involved in the development of diabetic cystopathy. METHODS: Bladder function was assessed in a streptozotocin (STZ)-induced diabetic rat model with or without 3-aminobenzamide treatment, a PARP inhibitor. The degree of bladder apoptosis, expression of poly(ADP-ribose) (PAR) in the bladder, phosphorylated JNK, the levels of Bcl-2 and Bax, caspase 3 activity and nuclear translocation of the apoptotic inducing factor (AIF) from mitochondria were investigated. RESULTS: Bladder dysfunction was significantly associated with an increase of bladder apoptosis, and a reduction of the Bcl-2/Bax ratio. In addition, the amount of PAR, phosphorylated JNK, caspase 3 activity, and nuclear translocation of AIF were significantly increased in the diabetic rats. Inhibition of PARP significantly suppressed activation of PARP, JNK and restored the Bcl-2/Bax ratio. Activation of caspase 3 and nuclear translocation of AIF were also significantly reduced by PARP inhibition. As a result, the bladder apoptosis was attenuated and the bladder function improved. CONCLUSIONS: These results indicate that bladder apoptosis is involved in diabetic cystopathy via activation of the PARP/JNK/mitochondrial apoptotic pathway. These findings may be used to develop novel therapies for patients with diabetic bladder dysfunction.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Aifm1  (apoptosis inducing factor, mitochondria associated 1)

Genes (Mus musculus)
Aifm1  (apoptosis-inducing factor, mitochondrion-associated 1)

Genes (Homo sapiens)
AIFM1  (apoptosis inducing factor mitochondria associated 1)


Additional Information