PMID- 32230890
OWN - NLM
STAT- MEDLINE
DCOM- 20210113
LR  - 20210113
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 25
IP  - 7
DP  - 2020 Mar 27
TI  - Lysophosphatidic Acid Inhibits Simvastatin-Induced Myocytoxicity by Activating 
      LPA Receptor/PKC Pathway.
LID - 10.3390/molecules25071529 [doi]
LID - 1529
AB  - Statins such as simvastatin have many side effects, including muscle damage, 
      which is known to be the most frequent undesirable side effect. Lysophosphatidic 
      acid (LPA), a kind of biolipid, has diverse cellular activities, including cell 
      proliferation, survival, and migration. However, whether LPA affects 
      statin-linked muscle damage has not been reported yet. In the present study, to 
      determine whether LPA might exert potential protective effect on statin-induced 
      myocyotoxicity, the effect of LPA on cytotoxicity in rat L6 myoblasts exposed to 
      simvastatin was explored. Viability and apoptosis of rat L6 myoblasts were 
      detected via 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5- 
      [(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay and terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, 
      respectively. Protein expression levels were detected via Western blotting. 
      Simvastatin decreased viability of L6 cells. Such decrease in viability was 
      recovered in the presence of LPA. Treatment with LPA suppressed 
      simvastatin-induced apoptosis in L6 cells. In addition, treatment with LPA 
      receptor inhibitor Ki16425, protein kinase C (PKC) inhibitor GF109203X, or 
      intracellular calcium chelator BAPTA-AM attenuated the recovery effect of LPA on 
      simvastatin-induced L6 cell toxicity. These findings indicate that LPA may 
      inhibit simvastatin-induced toxicity in L6 cells probably by activating the LPA 
      receptor-PKC pathway. Therefore, LPA might have potential as a bioactive molecule 
      to protect muscles against simvastatin-induced myotoxicity.
FAU - Won, Kyung-Jong
AU  - Won KJ
AD  - Department of Physiology and Medical Science, School of Medicine, Konkuk 
      University, Chungju 27478, Korea.
FAU - Goh, Yu-Jin
AU  - Goh YJ
AD  - Department of Pharmaceutical Engineering, College of Health Sciences, Sangji 
      University, Wonju 26339, Korea.
FAU - Hwang, Sung-Hee
AU  - Hwang SH
AD  - Department of Pharmaceutical Engineering, College of Health Sciences, Sangji 
      University, Wonju 26339, Korea.
LA  - eng
GR  - Sangji University 2018 to S.-H. Hwang/Sangji University/
GR  - NRF-2017R1D1A1B03031395/The Ministry of Education, Republic of Korea/
GR  - NRF-2017R1D1A1B03035674/the Ministry of Education, Republic of Korea/
PT  - Journal Article
DEP - 20200327
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) 
      benzylsulfanyl) propanoic acid)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Isoxazoles)
RN  - 0 (Lysophospholipids)
RN  - 0 (Maleimides)
RN  - 0 (Propionates)
RN  - 0 (Receptors, Lysophosphatidic Acid)
RN  - 0 (bcl-2-Associated X Protein)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.22.- (Caspase 3)
RN  - L79H6N0V6C (bisindolylmaleimide I)
RN  - PG6M3969SG (lysophosphatidic acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Calcium/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/pharmacology
MH  - Indoles/pharmacology
MH  - Isoxazoles/pharmacology
MH  - Lysophospholipids/*pharmacology
MH  - Maleimides/pharmacology
MH  - Myoblasts/*drug effects/metabolism
MH  - Propionates/pharmacology
MH  - Protein Kinase C/antagonists & inhibitors/*metabolism
MH  - Rats
MH  - Receptors, Lysophosphatidic Acid/*antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - Simvastatin/*adverse effects/pharmacology
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC7180799
OTO - NOTNLM
OT  - L6 cells
OT  - cytotoxicity
OT  - lysophosphatidic acid
OT  - muscle cell
OT  - simvastatin
COIS- The authors declare no conflict of interest.
EDAT- 2020/04/02 06:00
MHDA- 2021/01/14 06:00
PMCR- 2020/03/27
CRDT- 2020/04/02 06:00
PHST- 2020/02/05 00:00 [received]
PHST- 2020/03/03 00:00 [revised]
PHST- 2020/03/25 00:00 [accepted]
PHST- 2020/04/02 06:00 [entrez]
PHST- 2020/04/02 06:00 [pubmed]
PHST- 2021/01/14 06:00 [medline]
PHST- 2020/03/27 00:00 [pmc-release]
AID - molecules25071529 [pii]
AID - molecules-25-01529 [pii]
AID - 10.3390/molecules25071529 [doi]
PST - epublish
SO  - Molecules. 2020 Mar 27;25(7):1529. doi: 10.3390/molecules25071529.