PMID- 38302971
OWN - NLM
STAT- MEDLINE
DCOM- 20240205
LR  - 20240320
IS  - 1478-811X (Electronic)
IS  - 1478-811X (Linking)
VI  - 22
IP  - 1
DP  - 2024 Feb 1
TI  - Mechanosensitive channel of large conductance enhances the mechanical 
      stretching-induced upregulation of glycolysis and oxidative metabolism in Schwann 
      cells.
PG  - 93
LID - 10.1186/s12964-024-01497-x [doi]
LID - 93
AB  - BACKGROUND: Physical exercise directly stretching the peripheral nerve promotes 
      nerve regeneration; however, its action mechanism remains elusive. Our present 
      study aimed to investigate the effects of mechanosensitive channel of large 
      conductance (MscL) activated by mechanical stretching on the cultured Schwann 
      cells (SCs) and explore the possible mechanism. METHODS: Primary SCs from 
      neonatal mice at 3-5 days of age were derived and transfected with the lentivirus 
      vector expressing a mutant version of MscL, MscL-G22S. We first detected the cell 
      viability and calcium ion (Ca(2+)) influx in the MscL-G22S-expressing SCs with 
      low-intensity mechanical stretching and the controls. Proteomic and energy 
      metabolomics analyses were performed to investigate the comprehensive effects of 
      MscL-G22S activation on SCs. Measurement of glycolysis- and oxidative 
      phosphorylation-related molecules and ATP production were respectively performed 
      to further validate the effects of MscL-G22S activation on SCs. Finally, the 
      roles of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin 
      (mTOR) signaling pathway in the mechanism of energy metabolism modulation of SCs 
      by MscL-G22S activation was investigated. RESULTS: Mechanical stretching-induced 
      MscL-G22S activation significantly increased the cell viability and Ca(2+) influx 
      into the SCs. Both the proteomic and targeted energy metabolomics analysis 
      indicated the upregulation of energy metabolism as the main action mechanism of 
      MscL-G22S-activation on SCs. MscL-G22S-activated SCs showed significant 
      upregulation of glycolysis and oxidative phosphorylation when SCs with stretching 
      alone had only mild upregulation of energy metabolism than those without stimuli. 
      MscL-G22S activation caused significant phosphorylation of the PI3K/AKT/mTOR 
      signaling pathway and upregulation of HIF-1alpha/c-Myc. Inhibition of PI3K abolished 
      the MscL-G22S activation-induced upregulation of HIF-1alpha/c-Myc signaling in SCs 
      and reduced the levels of glycolysis- and oxidative phosphorylation-related 
      substrates and mitochondrial activity. CONCLUSION: Mechanical stretching 
      activates MscL-G22S to significantly promote the energy metabolism of SCs and the 
      production of energic substrates, which may be applied to enhance nerve 
      regeneration via the glia-axonal metabolic coupling.
CI  - (c) 2024. The Author(s).
FAU - Shan, Fangzhen
AU  - Shan F
AD  - Medical Research Centre, Affiliated Hospital of Jining Medical University, 
      Jining, Shandong Province, China.
FAU - Zhang, Nannan
AU  - Zhang N
AD  - Department of Respiratory and Critical Care, Affiliated Hospital of Jining 
      Medical University, Jining, Shandong Province, China.
FAU - Yao, Xiaoying
AU  - Yao X
AD  - Medical Research Centre, Affiliated Hospital of Jining Medical University, 
      Jining, Shandong Province, China.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Neurology, Affiliated Hospital of Jining Medical University, 89 
      Guhuai Road, Jining City, Shandong Province, 272029, China.
FAU - Wang, Zihao
AU  - Wang Z
AD  - Cheeloo Medical College, Shandong University, Jinan, Shandong Province, China.
FAU - Zhang, Chuanji
AU  - Zhang C
AD  - College of Rehabilitation Medicine, Shandong University of Traditional Chinese 
      Medicine, Jinan, Shandong Province, China.
FAU - Wang, Yuzhong
AU  - Wang Y
AD  - Medical Research Centre, Affiliated Hospital of Jining Medical University, 
      Jining, Shandong Province, China. wangyuzhong_ni@163.com.
AD  - Department of Neurology, Affiliated Hospital of Jining Medical University, 89 
      Guhuai Road, Jining City, Shandong Province, 272029, China. 
      wangyuzhong_ni@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240201
PL  - England
TA  - Cell Commun Signal
JT  - Cell communication and signaling : CCS
JID - 101170464
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Signal Transduction
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Up-Regulation
MH  - Proteomics
MH  - Proto-Oncogene Proteins c-myc/metabolism
MH  - Glycolysis
MH  - Schwann Cells/metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Oxidative Stress
MH  - Mammals/metabolism
PMC - PMC10835878
OTO - NOTNLM
OT  - Energy metabolism
OT  - Mechanical stretching
OT  - Mechanosensitive channel of large conductance
OT  - Schwann cells
COIS- The authors declare no competing interests.
EDAT- 2024/02/02 06:43
MHDA- 2024/02/05 06:43
PMCR- 2024/02/01
CRDT- 2024/02/02 00:05
PHST- 2023/12/29 00:00 [received]
PHST- 2024/01/21 00:00 [accepted]
PHST- 2024/02/05 06:43 [medline]
PHST- 2024/02/02 06:43 [pubmed]
PHST- 2024/02/02 00:05 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - 10.1186/s12964-024-01497-x [pii]
AID - 1497 [pii]
AID - 10.1186/s12964-024-01497-x [doi]
PST - epublish
SO  - Cell Commun Signal. 2024 Feb 1;22(1):93. doi: 10.1186/s12964-024-01497-x.