RGD Reference Report - PARP inhibition restores erectile function by suppressing corporal smooth muscle apoptosis in diabetic rats. - Rat Genome Database

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PARP inhibition restores erectile function by suppressing corporal smooth muscle apoptosis in diabetic rats.

Authors: Li, WJ  Zhou, J  Li, B  Wang, H  Peng, YB  Wang, Z 
Citation: Li WJ, etal., J Sex Med. 2011 Apr;8(4):1072-82. doi: 10.1111/j.1743-6109.2010.02176.x. Epub 2011 Jan 14.
RGD ID: 10053666
Pubmed: PMID:21235725   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1743-6109.2010.02176.x   (Journal Full-text)

INTRODUCTION: An important mechanism suggested to be responsible for diabetes-associated erectile dysfunction (ED) involves increased apoptosis, increased collagen deposition, and reduced smooth muscle content in the corpus cavernosum. AIM: To determine whether the activation of the pro-apoptotic poly(adenosine diphosphate ribose) polymerase (PARP) pathway is involved in the induction of corporal apoptosis, and whether the administration of 3-aminobenzamide (3-AB), a specific PARP inhibitor, could ameliorate ED in diabetic rats. METHODS: Male Sprague-Dawley rats (8-weeks-old) were randomly divided into three groups: age-matched controls (C), diabetic controls (DM), and 3-AB-treated diabetic group (DM + 3-AB). Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (50 mg/kg). Eight weeks after the induction of diabetes, DM + 3-AB group treated with 3-AB (30 mg/kg/day, ip) for 4 weeks. MAIN OUTCOME MEASURES: At 12 weeks after diabetes induction, erectile function was assessed by cavernous nerve stimulation. Penile tissue was assessed for apoptosis, Masson's trichrome stain and immunohistochemical analysis for smooth muscle alpha actin. Expression of poly(ADP-ribose), phospho-protein kinase B (Akt), phospho-Bcl-2-associated death promoter (Bad), B-cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X Protein (Bax), and apoptosis-inducing factor (AIF) were evaluated by Western blot. Caspase-3 activity and malondialdehyde (MDA), adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide (NAD+) concentrations were also determined. RESULTS: DM group showed impaired erectile function, increased PARP activity and corporal apoptosis, and decreased smooth muscle contents. Expression of phospho-Akt, phospho-Bad, Bcl-2, and concentrations of ATP and NAD+ were decreased in the DM group, whereas concentrations of MDA, expression of Bax, nuclear translocation of AIF, and caspase-3 activity were increased. Treatment with 3-AB restored erectile function and significantly reversed all molecular and histological alterations except for the increased MDA. CONCLUSION: Over-activation of penile PARP pathway in diabetic rats enhances corporal apoptosis via energy depletion, suppression of Akt phosphorylation, and activation of the mitochondrial apoptotic pathway, which results in ED; these event could be prevented by treatment with 3-AB.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AKT1Humanimpotence treatmentISOAkt1 (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
Akt1Ratimpotence treatmentIDA associated with Diabetes Mellitus and ExperimentalRGD 
Akt1Mouseimpotence treatmentISOAkt1 (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
BADHumanimpotence treatmentISOBad (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
BAXHumanimpotence treatmentISOBax (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
BCL2Humanimpotence treatmentISOBcl2 (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
BadRatimpotence treatmentIDA associated with Diabetes Mellitus and ExperimentalRGD 
BadMouseimpotence treatmentISOBad (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
BaxRatimpotence treatmentIEP associated with Diabetes Mellitus and ExperimentalRGD 
BaxMouseimpotence treatmentISOBax (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
Bcl2Ratimpotence treatmentIEP associated with Diabetes Mellitus and ExperimentalRGD 
Bcl2Mouseimpotence treatmentISOBcl2 (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
CASP3Humanimpotence treatmentISOCasp3 (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
Casp3Ratimpotence treatmentIEP associated with Diabetes Mellitus and ExperimentalRGD 
Casp3Mouseimpotence treatmentISOCasp3 (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)
Bad  (BCL2-associated agonist of cell death)
Bax  (BCL2 associated X, apoptosis regulator)
Bcl2  (BCL2, apoptosis regulator)
Casp3  (caspase 3)

Genes (Mus musculus)
Akt1  (thymoma viral proto-oncogene 1)
Bad  (BCL2-associated agonist of cell death)
Bax  (BCL2-associated X protein)
Bcl2  (B cell leukemia/lymphoma 2)
Casp3  (caspase 3)

Genes (Homo sapiens)
AKT1  (AKT serine/threonine kinase 1)
BAD  (BCL2 associated agonist of cell death)
BAX  (BCL2 associated X, apoptosis regulator)
BCL2  (BCL2 apoptosis regulator)
CASP3  (caspase 3)


Additional Information