Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection
cAMP response element-binding (CREB) protein is a cellular transcription factor that mediates responses to different physiological and pathological signals. Using a model of human neuronal cells we demonstrate herein, that CREB is phosphorylated after oxidative stress induced by hydrogen peroxide. T...
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paper:paper_03008177_v425_n1-2_p9_Pregi2023-06-08T15:27:27Z Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection Pregi, Nicolás Cánepa, Eduardo Tomás Apoptosis CREB transcription factor DNA damage response Genotoxic stress Neuronal cells Phosphorylation caspase 3 cyclic AMP responsive element binding protein hydrogen peroxide CREB1 protein, human cyclic AMP dependent protein kinase cyclic AMP responsive element binding protein apoptosis Article cell cycle cell death cell survival controlled study DNA content DNA damage DNA damage response DNA repair flow cytometry fluorescence microscopy human human cell nerve cell nerve cell differentiation neuroblastoma cell neuroprotection oxidative stress protein phosphorylation regulatory mechanism reporter gene upregulation cell death DNA damage genetics metabolism nerve cell phosphorylation tumor cell line upregulation Cell Death Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Cyclic AMP-Dependent Protein Kinases DNA Damage DNA Repair Humans Neurons Oxidative Stress Phosphorylation Up-Regulation cAMP response element-binding (CREB) protein is a cellular transcription factor that mediates responses to different physiological and pathological signals. Using a model of human neuronal cells we demonstrate herein, that CREB is phosphorylated after oxidative stress induced by hydrogen peroxide. This phosphorylation is largely independent of PKA and of the canonical phosphoacceptor site at ser-133, and is accompanied by an upregulation of CREB expression at both mRNA and protein levels. In accordance with previous data, we show that CREB upregulation promotes cell survival and that its silencing results in an increment of apoptosis after oxidative stress. Interestingly, we also found that CREB promotes DNA repair after treatment with hydrogen peroxide. Using a cDNA microarray we found that CREB is responsible for the regulation of many genes involved in DNA repair and cell survival after oxidative injury. In summary, the neuroprotective effect mediated by CREB appears to follow three essential steps following oxidative injury. First, the upregulation of CREB expression that allows sufficient level of activated and phosphorylated protein is the primordial event that promotes the induction of genes of the DNA Damage Response. Then and when the DNA repair is effective, CREB induces detoxification and survival genes. This kinetics seems to be important to completely resolve oxidative-induced neuronal damages. © 2016, Springer Science+Business Media New York. Fil:Pregi, N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cánepa, E.T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v425_n1-2_p9_Pregi http://hdl.handle.net/20.500.12110/paper_03008177_v425_n1-2_p9_Pregi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Apoptosis CREB transcription factor DNA damage response Genotoxic stress Neuronal cells Phosphorylation caspase 3 cyclic AMP responsive element binding protein hydrogen peroxide CREB1 protein, human cyclic AMP dependent protein kinase cyclic AMP responsive element binding protein apoptosis Article cell cycle cell death cell survival controlled study DNA content DNA damage DNA damage response DNA repair flow cytometry fluorescence microscopy human human cell nerve cell nerve cell differentiation neuroblastoma cell neuroprotection oxidative stress protein phosphorylation regulatory mechanism reporter gene upregulation cell death DNA damage genetics metabolism nerve cell phosphorylation tumor cell line upregulation Cell Death Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Cyclic AMP-Dependent Protein Kinases DNA Damage DNA Repair Humans Neurons Oxidative Stress Phosphorylation Up-Regulation |
| spellingShingle |
Apoptosis CREB transcription factor DNA damage response Genotoxic stress Neuronal cells Phosphorylation caspase 3 cyclic AMP responsive element binding protein hydrogen peroxide CREB1 protein, human cyclic AMP dependent protein kinase cyclic AMP responsive element binding protein apoptosis Article cell cycle cell death cell survival controlled study DNA content DNA damage DNA damage response DNA repair flow cytometry fluorescence microscopy human human cell nerve cell nerve cell differentiation neuroblastoma cell neuroprotection oxidative stress protein phosphorylation regulatory mechanism reporter gene upregulation cell death DNA damage genetics metabolism nerve cell phosphorylation tumor cell line upregulation Cell Death Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Cyclic AMP-Dependent Protein Kinases DNA Damage DNA Repair Humans Neurons Oxidative Stress Phosphorylation Up-Regulation Pregi, Nicolás Cánepa, Eduardo Tomás Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection |
| topic_facet |
Apoptosis CREB transcription factor DNA damage response Genotoxic stress Neuronal cells Phosphorylation caspase 3 cyclic AMP responsive element binding protein hydrogen peroxide CREB1 protein, human cyclic AMP dependent protein kinase cyclic AMP responsive element binding protein apoptosis Article cell cycle cell death cell survival controlled study DNA content DNA damage DNA damage response DNA repair flow cytometry fluorescence microscopy human human cell nerve cell nerve cell differentiation neuroblastoma cell neuroprotection oxidative stress protein phosphorylation regulatory mechanism reporter gene upregulation cell death DNA damage genetics metabolism nerve cell phosphorylation tumor cell line upregulation Cell Death Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Cyclic AMP-Dependent Protein Kinases DNA Damage DNA Repair Humans Neurons Oxidative Stress Phosphorylation Up-Regulation |
| description |
cAMP response element-binding (CREB) protein is a cellular transcription factor that mediates responses to different physiological and pathological signals. Using a model of human neuronal cells we demonstrate herein, that CREB is phosphorylated after oxidative stress induced by hydrogen peroxide. This phosphorylation is largely independent of PKA and of the canonical phosphoacceptor site at ser-133, and is accompanied by an upregulation of CREB expression at both mRNA and protein levels. In accordance with previous data, we show that CREB upregulation promotes cell survival and that its silencing results in an increment of apoptosis after oxidative stress. Interestingly, we also found that CREB promotes DNA repair after treatment with hydrogen peroxide. Using a cDNA microarray we found that CREB is responsible for the regulation of many genes involved in DNA repair and cell survival after oxidative injury. In summary, the neuroprotective effect mediated by CREB appears to follow three essential steps following oxidative injury. First, the upregulation of CREB expression that allows sufficient level of activated and phosphorylated protein is the primordial event that promotes the induction of genes of the DNA Damage Response. Then and when the DNA repair is effective, CREB induces detoxification and survival genes. This kinetics seems to be important to completely resolve oxidative-induced neuronal damages. © 2016, Springer Science+Business Media New York. |
| author |
Pregi, Nicolás Cánepa, Eduardo Tomás |
| author_facet |
Pregi, Nicolás Cánepa, Eduardo Tomás |
| author_sort |
Pregi, Nicolás |
| title |
Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection |
| title_short |
Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection |
| title_full |
Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection |
| title_fullStr |
Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection |
| title_full_unstemmed |
Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection |
| title_sort |
oxidative stress-induced creb upregulation promotes dna damage repair prior to neuronal cell death protection |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v425_n1-2_p9_Pregi http://hdl.handle.net/20.500.12110/paper_03008177_v425_n1-2_p9_Pregi |
| work_keys_str_mv |
AT preginicolas oxidativestressinducedcrebupregulationpromotesdnadamagerepairpriortoneuronalcelldeathprotection AT canepaeduardotomas oxidativestressinducedcrebupregulationpromotesdnadamagerepairpriortoneuronalcelldeathprotection |
| _version_ |
1768543559608172544 |