Satellite Cells Say NO to Radiation

Jennie J Cho-Lim,Bertrand P Tseng,Charles L Limoli,Erich Giedzinski,Mike J Baker,Vincent J Caiozzo

doi:10.1667/rr2453.1

Abstract

Skeletal muscles are commonly exposed to radiation for diagnostic procedures and the treatment of cancers and heterotopic bone formation. Few studies have considered the impact of clinical doses of radiation on the ability of satellite cells (myogenic stem cells) to proliferate, differentiate and contribute to recovering/maintaining muscle mass. The primary objective of this study was to determine whether the proliferation of irradiated satellite cells could be rescued by manipulating NO levels via pharmacological approaches and mechanical stretch (which is known to increase NO levels). We used both SNP (NO donor) and PTIO (NO scavenger) to manipulate NO levels in satellite cells. We observed that SNP was highly effective in rescuing the proliferation of irradiated satellite cells, especially at doses less than 5 Gy. The potential importance of NO was further illustrated by the effects of PTIO, which completely inhibited the rescue effect of SNP. Mechanical cyclic stretch was found to produce significant increases in NO levels of irradiated satellite cells, and this was associated with a robust increase in satellite cell proliferation. The effects of both radiation and NO on two key myogenic regulatory factors (MyoD and myogenin) were also explored. Irradiation of satellite cells produced a significant increase in both MyoD and myogenin, effects that were mitigated by manipulating NO levels via SNP. Given the central role of myogenic regulatory factors in the proliferation and differentiation of satellite cells, the findings of the current study underscore the need to more fully understand the relationship between radiation, NO and the functionality of satellite cells.

Highlights

Satellite cells are myogenic stem cells that initially were discovered by Mauro [1], who observed their presence directly outside the cell membrane of individual muscle fibers
While skeletal muscle fibers are postmitotic and as a result are thought to be highly radioresistant, few studies have considered the impact of clinical doses of radiation on the ability of satellite cells to proliferate, differentiate and contribute to recovering/maintaining muscle mass
When SNP was used in combination with the NO scavenger PTIO (5 μM), DAF fluorescence was attenuated, indicating the ability of PTIO to reduce NO levels in satellite cells

Summary

Introduction

Satellite cells are myogenic stem cells that initially were discovered by Mauro [1], who observed their presence directly outside the cell membrane of individual muscle fibers (cells). While skeletal muscle fibers (cells) are postmitotic and as a result are thought to be highly radioresistant, few studies have considered the impact of clinical doses of radiation on the ability of satellite cells to proliferate, differentiate and contribute to recovering/maintaining muscle mass. This is an important consideration because a number of studies [12,13,14,15,16,17,18,19] have noted that muscle mass and function can be negatively affected after procedures involving radiation (e.g., treatment of breast/bone cancers)

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