Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth.
Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as i6A-) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRNA[Ser]Sec). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from i6A- mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were approximately 50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the i6A- mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase (p70S6k) (P < 0.05) before ablation, perhaps accounting for the enhanced response to synergist ablation. Thus, a single genetic alteration resulted in enhanced skeletal muscle adaptation after exercise, and this is likely through subtle changes in the resting phosphorylation state of growth-related kinases.
Hornberger
Troy A
TA
School of Kinesiology, University of Illinois, Chicago, IL 60608, USA.
McLoughlin
Thomas J
TJ
Leszczynski
Jori K
JK
Armstrong
Dustin D
DD
Jameson
Ruth R
RR
Bowen
Phyllis E
PE
Hwang
Eun-Sun
ES
Hou
Honglin
H
Moustafa
Mohamed E
ME
Carlson
Bradley A
BA
Hatfield
Dolph L
DL
Diamond
Alan M
AM
Esser
Karyn A
KA
D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000737:chemistry / Q000254:growth & development*; D009154:Mutation; D009929:Organ Size; D010766:Phosphorylation; D005082:Physical Exertion; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012643:Selenium / Q000172:deficiency* / Q000502:physiology; D051140:Selenoproteins; D015398:Signal Transduction
D011506:Proteins; D011518:Proto-Oncogene Proteins; D012345:RNA, Transfer, Amino Acid-Specific; D051140:Selenoproteins; C036928:tRNA, selenocysteine-; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D012643:Selenium