It is unknown whether loss of skeletal muscle mass and function experienced by astronauts during space flight could be augmented by ionizing radiation (IR), such as low-dose high-charge and energy (HZE) particles or low-dose high-energy proton radiation. In the current study adult mice were irradiated whole-body with either a single dose of 15 cGy of 1 GeV/n 56Fe-particle or with a 90 cGy proton of 1 GeV/n proton particles. Both ionizing radiation types caused alterations in the skeletal muscle cytoplasmic Ca2+ ([Ca2+]i) homeostasis. 56Fe-particle irradiation also caused a reduction of depolarization-evoked Ca2+ release from the sarcoplasmic reticulum (SR). The increase in the [Ca2+]i was detected as early as 24 h after 56Fe-particle irradiation, while effects of proton irradiation were only evident at 72 h. In both instances [Ca2+]i returned to baseline at day 7 after irradiation. All 56Fe-particle irradiated samples revealed a significant number of centrally localized nuclei, a histologic manifestation of regenerating muscle, 7 days after irradiation. Neither unirradiated control or proton-irradiated samples exhibited such a phenotype. Protein analysis revealed significant increase in the phosphorylation of Akt, Erk1/2 and rpS6k on day 7 in 56Fe-particle irradiated skeletal muscle, but not proton or unirradiated skeletal muscle, suggesting activation of pro-survival signaling. Our findings suggest that a single low-dose 56Fe-particle or proton exposure is sufficient to affect Ca2+ homeostasis in skeletal muscle. However, only 56Fe-particle irradiation led to the appearance of central nuclei and activation of pro-survival pathways, suggesting an ongoing muscle damage/recovery process.
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1 November 2013
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October 17 2013
Divergent Modification of Low-Dose 56Fe-Particle and Proton Radiation on Skeletal Muscle
Alexander Shtifman;
Alexander Shtifman
aCardiovascular Division and
cTufts University School of Medicine, Boston, Massachusetts, 02135; and
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Matthew J. Pezone;
Matthew J. Pezone
aCardiovascular Division and
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Sharath P. Sasi;
Sharath P. Sasi
aCardiovascular Division and
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Aleksandr Perepletchikov;
Aleksandr Perepletchikov
bDepartment of Pathology, Steward St. Elizabeth's Medical Center,
cTufts University School of Medicine, Boston, Massachusetts, 02135; and
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Xinhua Yan;
Xinhua Yan
aCardiovascular Division and
cTufts University School of Medicine, Boston, Massachusetts, 02135; and
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Raj Kishore;
Raj Kishore
dFeinberg Cardiovascular Research Institute, Northwestern University, Chicago, Illinois 60611
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David A. Goukassian
David A. Goukassian
1
aCardiovascular Division and
cTufts University School of Medicine, Boston, Massachusetts, 02135; and
1Address for correspondence: Tufts University School of Medicine, Steward St. Elizabeth's Medical Center, 736 Cambridge Street, CBR-340, Brighton, MA 02135; e-mail: [email protected] or [email protected].
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Radiat Res (2013) 180 (5): 455–464.
Article history
Received:
February 04 2013
Accepted:
July 12 2013
Citation
Alexander Shtifman, Matthew J. Pezone, Sharath P. Sasi, Akhil Agarwal, Hannah Gee, Jin Song, Aleksandr Perepletchikov, Xinhua Yan, Raj Kishore, David A. Goukassian; Divergent Modification of Low-Dose 56Fe-Particle and Proton Radiation on Skeletal Muscle. Radiat Res 1 November 2013; 180 (5): 455–464. doi: https://doi.org/10.1667/RR3329.1
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