The radiosensitivity of satellite cells: cell cycle regulation, apoptosis and oxidative stress.
Skeletal muscles are the organ of movement, and their growth, regeneration and maintenance are dependent in large part on a population of myogenic stem cells known as satellite cells. Skeletal muscles and these resident myogenic stem cells (i.e., satellite cells) are commonly exposed to significant doses of radiation during diagnostic procedures and/or during the radiotherapeutic management of cancer. The main objective of this study was to examine the effects of clinically relevant doses of γ radiation on satellite cell survival and proliferation, cell cycle regulation, apoptosis, DNA double-strand break repair, oxidative stress and NO production. Overall, our findings demonstrate that doses of γ radiation ≥5 Gy reduced satellite cell numbers by at least 70% due in part to elevated apoptosis and the inhibition of cell cycle progression. Radiation was also found to cause a significant and persistent increase in the level of reactive oxygen and nitrogen species. Interestingly, and within this backdrop of elevated oxidative stress, similar doses were found to produce substantial reductions in the levels of nitric oxide (NO). Proliferation of satellite cells has been shown to depend in part on the production of NO, and our findings give rise to the possibility that radiation-induced reductions in NO levels may provide a mechanism for the inhibition of satellite cell proliferation in vitro and possibly the regrowth of skeletal muscle exposed during clinical irradiation procedures.
Caiozzo
Vincent J
VJ
Department of Orthopaedics, School of Medicine, University of California, Irvine, California 92697, USA. vjcaiozz@uci.edu
Giedzinski
Erich
E
Baker
Mike
M
Suarez
Tatiana
T
Izadi
Atefeh
A
Lan
Mary
M
Cho-Lim
Jennie
J
Tseng
Bertrand P
BP
Limoli
Charles L
CL
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000528:radiation effects*; D051381:Rats; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D015398:Signal Transduction / Q000528:radiation effects
D006657:Histones; D009569:Nitric Oxide