SOD3 Decreases Ischemic Injury Derived Apoptosis through Phosphorylation of Erk1/2, Akt, and FoxO3a
| Autor: | Massimo Santoro, Lilja E. Laatikainen, Maria Domenica Castellone, Juha P. Laurila, Mikko O. Laukkanen, Mariarosaria Incoronato |
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| Přispěvatelé: | Laatikainen, Le, Incoronato, M, Castellone, Md, Laurila, Jp, Santoro, Massimo, Laukkanen, M. O. |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Apoptosis Signal transduction ERK signaling cascade Cardiovascular chemistry.chemical_compound Mice 0302 clinical medicine Molecular cell biology Akt signaling cascade Ischemia oxidative stress Phosphorylation Extracellular Signal-Regulated MAP Kinases Cellular Stress Responses Peripheral Vascular Diseases Mitogen-Activated Protein Kinase 1 0303 health sciences Multidisciplinary Mitogen-Activated Protein Kinase 3 biology Cell Death Superoxide Forkhead Box Protein O3 Signaling cascades Forkhead Transcription Factors Cell biology 030220 oncology & carcinogenesis Medicine signaling Research Article SOD3 Cell Survival MAP Kinase Signaling System Science Models Biological Superoxide dismutase 03 medical and health sciences Apoptotic signaling cascade oncogenesi Animals Protein kinase B Biology 030304 developmental biology Superoxide Dismutase Rats Inbred F344 Rats chemistry Cell culture biology.protein NIH 3T3 Cells Proto-Oncogene Proteins c-akt |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 8, p e24456 (2011) PloS one 6 (2011). doi:10.1371/journal.pone.0024456 info:cnr-pdr/source/autori:Laatikainen, LE [ 1 ] ; Incoronato, M [ 2 ] ; Castellone, MD [ 3 ] ; Laurila, JP [ 1 ] ; Santoro, M [ 3 ] ; Laukkanen, MO [ 1,2]/titolo:SOD3 Decreases Ischemic Injury Derived Apoptosis through Phosphorylation of Erk1%2F2, Akt, and FoxO3a./doi:10.1371%2Fjournal.pone.0024456/rivista:PloS one/anno:2011/pagina_da:/pagina_a:/intervallo_pagine:/volume:6 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0024456 |
| Popis: | BackgroundExtracellular superoxide dismutase (SOD3), which dismutates superoxide anion to hydrogen peroxide, has been shown to reduce the free radical stress derived apoptosis in tissue injuries. Since both superoxide anion and hydrogen peroxide have a marked impact on signal transduction pathways and could potentially explain a number of apoptosis and survival -related phenomena in different pathological conditions, we clarified the impact of SOD3 on Akt and Erk1/2 cell survival pathways in rat hind limb injury model.Methodology and principal findingsBased on our data, the hind limb ischemic rats treated with virally delivered sod3 have milder injury and less apoptosis than control animals that could be due to parallel activation of pro-proliferative and anti-apoptotic Erk1/2 and Akt pathways. The common downstream factor of both signaling pathways, the apoptosis related forkhead box protein O3a (FoxO3a), was phosphorylated and translocated to the cytoplasm in sod3 treated tissues and cell line. Additionally, we obtained increased mRNA production of elk-1, ets-1, and microRNA 21 (miR-21), whereas synthesis of bim mRNA was decreased in sod3 overexpressing tissues. We further showed that overexpression of sod3 modulated redox related gene expression by downregulating nox2 and inos when compared to injured control animals.Conclusions and significanceThe study shows the complexity of SOD3-derived effects on tissue injury recovery that are not limited to the reduction of superoxide anion caused cellular stress but highlights the impact of SOD3 related signal transduction on tissue functions and suggests an important role for SOD3 in attenuating cell stress effects in different pathological conditions. |
| Databáze: | OpenAIRE |
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