Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models
Ionizing radiation is widely used in medicine and is valuable in both the diagnosis and treatment of many diseases. However, its health effects are ambiguous. Here, we report that low-dose ionizing radiation has beneficial effects in human amyloid-β42 (Aβ42)-expressing Drosophila Alzheimer's di...
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| Format: | Article |
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The Company of Biologists
2019-02-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/8/2/bio036657 |
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| author | Soojin Hwang Haemin Jeong Eun-Hee Hong Hae Mi Joo Kyoung Sang Cho Seon Young Nam |
| author_facet | Soojin Hwang Haemin Jeong Eun-Hee Hong Hae Mi Joo Kyoung Sang Cho Seon Young Nam |
| author_sort | Soojin Hwang |
| collection | DOAJ |
| description | Ionizing radiation is widely used in medicine and is valuable in both the diagnosis and treatment of many diseases. However, its health effects are ambiguous. Here, we report that low-dose ionizing radiation has beneficial effects in human amyloid-β42 (Aβ42)-expressing Drosophila Alzheimer's disease (AD) models. Ionizing radiation at a dose of 0.05 Gy suppressed AD-like phenotypes, including developmental defects and locomotive dysfunction, but did not alter the decreased survival rates and longevity of Aβ42-expressing flies. The same dose of γ-irradiation reduced Aβ42-induced cell death in Drosophila AD models through downregulation of head involution defective (hid), which encodes a protein that activates caspases. However, 4 Gy of γ-irradiation increased Aβ42-induced cell death without modulating pro-apoptotic genes grim, reaper and hid. The AKT signaling pathway, which was suppressed in Drosophila AD models, was activated by either 0.05 or 4 Gy γ-irradiation. Interestingly, p38 mitogen-activated protein-kinase (MAPK) activity was inhibited by exposure to 0.05 Gy γ-irradiation but enhanced by exposure to 4 Gy in Aβ42-expressing flies. In addition, overexpression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT signaling pathway, or a null mutant of AKT strongly suppressed the beneficial effects of low-dose ionizing radiation in Aβ42-expressing flies. These results indicate that low-dose ionizing radiation suppresses Aβ42-induced cell death through regulation of the AKT and p38 MAPK signaling pathways, suggesting that low-dose ionizing radiation has hormetic effects on the pathogenesis of Aβ42-associated AD. |
| first_indexed | 2024-12-18T00:06:09Z |
| format | Article |
| id | doaj.art-43eb9b7466e0468782ebe12a9deb285c |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-18T00:06:09Z |
| publishDate | 2019-02-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-43eb9b7466e0468782ebe12a9deb285c2022-12-21T21:27:47ZengThe Company of BiologistsBiology Open2046-63902019-02-018210.1242/bio.036657036657Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease modelsSoojin Hwang0Haemin Jeong1Eun-Hee Hong2Hae Mi Joo3Kyoung Sang Cho4Seon Young Nam5 Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seoul 01450, Korea Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seoul 01450, Korea Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seoul 01450, Korea Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seoul 01450, Korea Department of Biological Sciences, Konkuk University, Seoul 05029, Korea Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seoul 01450, Korea Ionizing radiation is widely used in medicine and is valuable in both the diagnosis and treatment of many diseases. However, its health effects are ambiguous. Here, we report that low-dose ionizing radiation has beneficial effects in human amyloid-β42 (Aβ42)-expressing Drosophila Alzheimer's disease (AD) models. Ionizing radiation at a dose of 0.05 Gy suppressed AD-like phenotypes, including developmental defects and locomotive dysfunction, but did not alter the decreased survival rates and longevity of Aβ42-expressing flies. The same dose of γ-irradiation reduced Aβ42-induced cell death in Drosophila AD models through downregulation of head involution defective (hid), which encodes a protein that activates caspases. However, 4 Gy of γ-irradiation increased Aβ42-induced cell death without modulating pro-apoptotic genes grim, reaper and hid. The AKT signaling pathway, which was suppressed in Drosophila AD models, was activated by either 0.05 or 4 Gy γ-irradiation. Interestingly, p38 mitogen-activated protein-kinase (MAPK) activity was inhibited by exposure to 0.05 Gy γ-irradiation but enhanced by exposure to 4 Gy in Aβ42-expressing flies. In addition, overexpression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT signaling pathway, or a null mutant of AKT strongly suppressed the beneficial effects of low-dose ionizing radiation in Aβ42-expressing flies. These results indicate that low-dose ionizing radiation suppresses Aβ42-induced cell death through regulation of the AKT and p38 MAPK signaling pathways, suggesting that low-dose ionizing radiation has hormetic effects on the pathogenesis of Aβ42-associated AD.http://bio.biologists.org/content/8/2/bio036657Amyloid-β42Alzheimer's diseaseDrosophilaLow-dose ionizing radiation |
| spellingShingle | Soojin Hwang Haemin Jeong Eun-Hee Hong Hae Mi Joo Kyoung Sang Cho Seon Young Nam Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models Biology Open Amyloid-β42 Alzheimer's disease Drosophila Low-dose ionizing radiation |
| title | Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models |
| title_full | Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models |
| title_fullStr | Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models |
| title_full_unstemmed | Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models |
| title_short | Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models |
| title_sort | low dose ionizing radiation alleviates aβ42 induced cell death via regulating akt and p38 pathways in drosophila alzheimer s disease models |
| topic | Amyloid-β42 Alzheimer's disease Drosophila Low-dose ionizing radiation |
| url | http://bio.biologists.org/content/8/2/bio036657 |
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