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.

Late Effects of Radiation on Skeletal Muscle: An Open Field of Research

“…From 33 studies included in this review, only six [14] [18]- [22] mentioned that they conducted randomization of samples, while other three studies did not specify the type of radiation applied in their experiments [23]- [25].…”

“…The study of Shtifman and coworkers [22] sought to investigate the effects of single whole-body low-dose high-energy proton irradiation as a model for solar particle event and low-dose high-charge and energy irradiation as a model for galactic cosmic rays on skeletal muscle physiology in adult C57Bl/6N WT mice. The data indicated that proton and 56 Fe-particle irradiation resulted in intra-myofiber alterations in Ca 2+ .…”

“…Based on the principle that randomization as the best way to avoid bias, only six studies [14] [18]- [22] performed their investigation taking into account the randomization of samples.…”

“…These events interfere in the lipid-protein interactions, which are essential for the functional activity of this enzyme. A study [22] concerning molecular analyses within 24 h post-irradiation [41], it was observed a significant rise of the resting cytoplasmic Ca 2+ and a reduction in the depolarization-evoked Ca 2+ released from the sarcoplasmic reticulum, suggesting the correlation of these results with the potential functional changes in the muscle excitation-contraction coupling.…”

Influence of longitudinal radiation exposure from microcomputed tomography scanning on skeletal muscle function and metabolic activity in female CD-1 mice

“…2009) and flexor digitorum brevis 7 days postexposure (Shtifman et al. 2013). Based on these studies, it appears that the impact of low‐dose radiation on skeletal muscle may be dependent on the source and the effects are somewhat acute and dissipate after 2–3 months.…”