RGD Reference Report - Apaf-1 inhibitors protect from unwanted cell death in in vivo models of kidney ischemia and chemotherapy induced ototoxicity. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Apaf-1 inhibitors protect from unwanted cell death in in vivo models of kidney ischemia and chemotherapy induced ototoxicity.

Authors: Orzáez, Mar  Sancho, Mónica  Marchán, Sandra  Mondragón, Laura  Montava, Rebeca  Valero, Juan García  Landeta, Olatz  Basañez, Gorka  Carbajo, Rodrigo J  Pineda-Lucena, Antonio  Bujons, Jordi  Moure, Alejandra  Messeguer, Angel  Lagunas, Carmen  Herrero, Carmen  Pérez-Payá, Enrique 
Citation: Orzáez M, etal., PLoS One. 2014 Oct 20;9(10):e110979. doi: 10.1371/journal.pone.0110979. eCollection 2014.
RGD ID: 13703111
Pubmed: PMID:25330150   (View Abstract at PubMed)
PMCID: PMC4203855   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0110979   (Journal Full-text)


BACKGROUND: Excessive apoptosis induces unwanted cell death and promotes pathological conditions. Drug discovery efforts aimed at decreasing apoptotic damage initially targeted the inhibition of effector caspases. Although such inhibitors were effective, safety problems led to slow pharmacological development. Therefore, apoptosis inhibition is still considered an unmet medical need.
METHODOLOGY AND PRINCIPAL FINDINGS: The interaction between Apaf-1 and the inhibitors was confirmed by NMR. Target specificity was evaluated in cellular models by siRNa based approaches. Cell recovery was confirmed by MTT, clonogenicity and flow cytometry assays. The efficiency of the compounds as antiapoptotic agents was tested in cellular and in vivo models of protection upon cisplatin induced ototoxicity in a zebrafish model and from hypoxia and reperfusion kidney damage in a rat model of hot ischemia.
CONCLUSIONS: Apaf-1 inhibitors decreased Cytc release and apoptosome-mediated activation of procaspase-9 preventing cell and tissue damage in ex vivo experiments and in vivo animal models of apoptotic damage. Our results provide evidence that Apaf-1 pharmacological inhibition has therapeutic potential for the treatment of apoptosis-related diseases.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
APAF1HumanRenal Ischemia treatmentISOApaf1 (Rattus norvegicus) RGD 
Apaf1RatRenal Ischemia treatmentIMP  RGD 
Apaf1MouseRenal Ischemia treatmentISOApaf1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Apaf1  (apoptotic peptidase activating factor 1)

Genes (Mus musculus)
Apaf1  (apoptotic peptidase activating factor 1)

Genes (Homo sapiens)
APAF1  (apoptotic peptidase activating factor 1)


Additional Information