PMID- 32791090
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20211204
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Linking)
VI  - 177
DP  - 2020 Oct
TI  - Diacylglycerol kinase eta regulates C2C12 myoblast proliferation through the mTOR 
      signaling pathway.
PG  - 13-24
LID - S0300-9084(20)30172-3 [pii]
LID - 10.1016/j.biochi.2020.07.018 [doi]
AB  - Diacylglycerol kinase (DGK) phosphorylates diacylglycerol to produce phosphatidic 
      acid (PA). The eta isozyme of DGK is abundantly expressed in C2C12 myoblasts. 
      However, the role of DGKeta in skeletal muscle cells remains unknown. In the 
      present study, we showed that DGKeta was downregulated at an early stage of 
      myogenic differentiation. The knockdown of DGKeta by siRNAs significantly inhibited 
      C2C12 myoblast proliferation but did not inhibit differentiation. Moreover, the 
      suppression of DGKeta expression decreased the expression levels of mammalian 
      target of rapamycin (mTOR), which is a key regulator of cell proliferation, and 
      fatty acid synthase (FASN), which catalyzes the de novo synthesis of fatty acids 
      for cell proliferation and is transcriptionally regulated via mTOR signaling. 
      Furthermore, the knockdown of mTOR or raptor, which is a component of mTOR 
      complex 1 (mTORC1), decreased the amount of FASN. These results indicate that 
      DGKeta regulates myoblast proliferation through the mTOR (mTORC1)-FASN pathway. 
      Interestingly, the knockdown of mTOR reduced the expression levels of DGKeta, 
      implying mutual regulation between DGKeta and mTOR. In DGKeta-knockdown myoblasts, 
      C30-C36-PA species, mTOR activators, were decreased, suggesting that the 
      modulation of mTOR activity through these PA species also plays an important role 
      in myoblast proliferation.
CI  - Copyright (c) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie 
      Moleculaire (SFBBM). All rights reserved.
FAU - Sakai, Hiromichi
AU  - Sakai H
AD  - Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center 
      for Science Research, Organization for Research and Academic Information, Shimane 
      University, Izumo, Japan. Electronic address: hisakai@med.shimane-u.ac.jp.
FAU - Murakami, Chiaki
AU  - Murakami C
AD  - Department of Chemistry, Graduate School of Science, Chiba University, Chiba, 
      Japan.
FAU - Usuki, Takako
AU  - Usuki T
AD  - Department of Chemistry, Graduate School of Science, Chiba University, Chiba, 
      Japan.
FAU - Lu, Qiang
AU  - Lu Q
AD  - Department of Chemistry, Graduate School of Science, Chiba University, Chiba, 
      Japan.
FAU - Matsumoto, Ken-Ichi
AU  - Matsumoto KI
AD  - Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center 
      for Science Research, Organization for Research and Academic Information, Shimane 
      University, Izumo, Japan.
FAU - Urano, Takeshi
AU  - Urano T
AD  - Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center 
      for Science Research, Organization for Research and Academic Information, Shimane 
      University, Izumo, Japan; Department of Biochemistry, Shimane University School 
      of Medicine, Izumo, Japan.
FAU - Sakane, Fumio
AU  - Sakane F
AD  - Department of Chemistry, Graduate School of Science, Chiba University, Chiba, 
      Japan. Electronic address: sakane@faculty.chiba-u.jp.
LA  - eng
PT  - Journal Article
DEP - 20200811
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (Diglycerides)
RN  - 0 (Phosphatidic Acids)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Rptor protein, mouse)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.3.1.85 (Fasn protein, mouse)
RN  - EC 2.3.1.85 (Fatty Acid Synthase, Type I)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.1.107 (Dgkh protein, mouse)
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mapk1 protein, mouse)
RN  - EC 2.7.11.24 (Mapk3 protein, mouse)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Cell Proliferation/genetics
MH  - Diacylglycerol Kinase/genetics/*metabolism
MH  - Diglycerides/metabolism
MH  - Down-Regulation
MH  - Fatty Acid Synthase, Type I/biosynthesis
MH  - Gene Knockdown Techniques
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Muscle Development/genetics
MH  - Myoblasts/metabolism
MH  - Phosphatidic Acids/chemistry/metabolism
MH  - Phosphorylation
MH  - Rapamycin-Insensitive Companion of mTOR Protein/genetics/metabolism
MH  - Regulatory-Associated Protein of mTOR/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Diacylglycerol kinase
OT  - Fatty acid synthase
OT  - Myoblast proliferation
OT  - Skeletal muscle
OT  - mTOR
COIS- Declaration of competing interest The authors declare no conflicts of interest.
EDAT- 2020/08/14 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/08/14 06:00
PHST- 2020/04/22 00:00 [received]
PHST- 2020/06/16 00:00 [revised]
PHST- 2020/07/27 00:00 [accepted]
PHST- 2020/08/14 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/08/14 06:00 [entrez]
AID - S0300-9084(20)30172-3 [pii]
AID - 10.1016/j.biochi.2020.07.018 [doi]
PST - ppublish
SO  - Biochimie. 2020 Oct;177:13-24. doi: 10.1016/j.biochi.2020.07.018. Epub 2020 Aug 
      11.