title: Divergent modification of low-dose ⁵⁶Fe-particle and proton radiation on skeletal muscle.
abstract: 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.
authors.affiliation: a Cardiovascular Division and.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shtifman
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Pezone
authors.forename: Sharath P
authors.initials: SP
authors.lastname: Sasi
authors.forename: Akhil
authors.initials: A
authors.lastname: Agarwal
authors.forename: Hannah
authors.initials: H
authors.lastname: Gee
authors.forename: Jin
authors.initials: J
authors.lastname: Song
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Perepletchikov
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yan
authors.forename: Raj
authors.initials: R
authors.lastname: Kishore
authors.forename: David A
authors.initials: DA
authors.lastname: Goukassian
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003359:Cosmic Radiation; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D006371:Helium / Q000737:chemistry; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000528:radiation effects*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D019445:Solar Activity
chemical_list: D006371:Helium; D002118:Calcium