PMID- 31624287
OWN - NLM
STAT- MEDLINE
DCOM- 20201106
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Oct 17
TI  - Simulated microgravity inhibits C2C12 myogenesis via phospholipase D2-induced 
      Akt/FOXO1 regulation.
PG  - 14910
LID - 10.1038/s41598-019-51410-7 [doi]
LID - 14910
AB  - The skeletal muscle system has evolved to maintain body posture against a 
      constant gravitational load. Mammalian target of rapamycin (mTOR) regulates the 
      mechanically induced increase in the skeletal muscle mass. In the present study, 
      we investigated mTOR pathway in C2C12 myoblasts in a model of mechanical 
      unloading by creating a simulated microgravity (SM) using 3 D clinorotation. SM 
      decreased the phosphorylation of Akt at Ser 473, which was mediated by mTOR 
      complex 2 (mTORC2), in C2C12 myoblasts, leading to a decrease in the cell growth 
      rate. Subsequently, SM inhibited C2C12 myogenesis in an Akt-dependent manner. In 
      addition, SM increased the phospholipase D (PLD) activity by enhancing PLD2 
      expression, resulting in the dissociation of mSIN1 from the mTORC2, followed by 
      decrease in the phosphorylation of Akt at Ser 473, and FOXO1 at Ser 256 in C2C12 
      myoblasts. Exposure to SM decreased the autophagic flux of C2C12 myoblasts by 
      regulation of mRNA level of autophagic genes in a PLD2 and FOXO1-dependent 
      manner, subsequently, resulting in a decrease in the C2C12 myogenesis. In 
      conclusion, by analyzing the molecular signature of C2C12 myogenesis using SM, we 
      suggest that the regulatory axis of the PLD2 induced Akt/FOXO1, is critical for 
      C2C12 myogenesis.
FAU - Baek, Mi-Ock
AU  - Baek MO
AD  - Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 
      21999, Republic of Korea.
AD  - Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, 
      Republic of Korea.
AD  - Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 
      21999, Republic of Korea.
FAU - Ahn, Chi Bum
AU  - Ahn CB
AD  - Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 
      21999, Republic of Korea.
FAU - Cho, Hye-Jeong
AU  - Cho HJ
AD  - Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, 
      Republic of Korea.
AD  - Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 
      21999, Republic of Korea.
FAU - Choi, Ji-Young
AU  - Choi JY
AD  - Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, 
      Republic of Korea.
AD  - Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 
      21999, Republic of Korea.
FAU - Son, Kuk Hui
AU  - Son KH
AD  - Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical 
      Center, College of Medicine, Gachon University, Incheon, 21565, Republic of 
      Korea. dr632@gilhospital.com.
FAU - Yoon, Mee-Sup
AU  - Yoon MS
AUID- ORCID: 0000-0002-0114-1142
AD  - Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 
      21999, Republic of Korea. msyoon@gachon.ac.kr.
AD  - Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, 
      Republic of Korea. msyoon@gachon.ac.kr.
AD  - Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 
      21999, Republic of Korea. msyoon@gachon.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191017
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Foxo1 protein, mouse)
RN  - EC 2.7.11.1 (Akt1 protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.4.- (phospholipase D2)
RN  - EC 3.1.4.4 (Phospholipase D)
SB  - IM
MH  - Animals
MH  - Cell Culture Techniques/methods
MH  - Cell Differentiation/physiology
MH  - Cell Line
MH  - Forkhead Box Protein O1/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/metabolism
MH  - Mice
MH  - Muscle Development/*physiology
MH  - Myoblasts/*physiology
MH  - Phospholipase D/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/physiology
MH  - Weightlessness Simulation/*adverse effects/methods
PMC - PMC6797799
COIS- The authors declare no competing interests.
EDAT- 2019/10/19 06:00
MHDA- 2020/11/11 06:00
PMCR- 2019/10/17
CRDT- 2019/10/19 06:00
PHST- 2019/04/02 00:00 [received]
PHST- 2019/09/30 00:00 [accepted]
PHST- 2019/10/19 06:00 [entrez]
PHST- 2019/10/19 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2019/10/17 00:00 [pmc-release]
AID - 10.1038/s41598-019-51410-7 [pii]
AID - 51410 [pii]
AID - 10.1038/s41598-019-51410-7 [doi]
PST - epublish
SO  - Sci Rep. 2019 Oct 17;9(1):14910. doi: 10.1038/s41598-019-51410-7.