PMID- 29446045
OWN - NLM
STAT- MEDLINE
DCOM- 20181031
LR  - 20211204
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 448
IP  - 1-2
DP  - 2018 Nov
TI  - Effects of extracellular orotic acid on acute contraction-induced adaptation 
      patterns in C2C12 cells.
PG  - 251-263
LID - 10.1007/s11010-018-3330-z [doi]
AB  - Dietary administration of orotic acid (OA), an intermediate in the pyrimidine 
      biosynthetic pathway, is considered to provide a wide range of beneficial 
      effects, including cardioprotection and exercise adaptation. Its mechanisms of 
      action, when applied extracellularly, however, are barely understood. In this 
      study, we evaluated potential effects of OA on skeletal muscle using an in vitro 
      contraction model of electrically pulse-stimulated (EPS) C2C12 myotubes. By 
      analyzing a subset of genes representing inflammatory, metabolic, and structural 
      adaptation pathways, we could show that OA supplementation diminishes the 
      EPS-provoked expression of inflammatory transcripts (interleukin 6, Il6; 
      chemokine (C-X-C Motif) ligand 5, Cxcl5), and attenuated transcript levels of 
      nuclear receptor subfamily 4 group A member 3 (Nr4A3), early growth response 1 
      (Egr1), activating transcription factor 3 (Atf3), and fast-oxidative MyHC-IIA 
      isoform (Myh2). By contrast, OA had no suppressive effect on the 
      pathogen-provoked inflammatory gene response in skeletal muscle cells, as 
      demonstrated by stimulation of C2C12 myotubes with bacterial LPS. In addition, we 
      observed a suppressive effect of OA on EPS-induced phosphorylation of 
      AMP-activated protein kinase (AMPK), whereas EPS-triggered 
      phosphorylation/activation of the mammalian target of rapamycin (mTOR) was not 
      affected. Finally, we demonstrate that OA positively influences glycogen levels 
      in EP-stimulated myotubes. Taken together, our results suggest that in skeletal 
      muscle cells, OA modulates both the inflammatory and the metabolic reaction 
      provoked by acute contraction. These results might have important clinical 
      implications, specifically in cardiovascular and exercise medicine.
FAU - Beiter, Thomas
AU  - Beiter T
AD  - Medical Clinic, Department of Sports Medicine, University Hospital Tubingen, 
      Hoppe-Seyler-Str. 6, 72076, Tubingen, Germany.
FAU - Hudemann, Jens
AU  - Hudemann J
AD  - Medical Clinic, Department of Sports Medicine, University Hospital Tubingen, 
      Hoppe-Seyler-Str. 6, 72076, Tubingen, Germany.
FAU - Burgstahler, Christof
AU  - Burgstahler C
AD  - Medical Clinic, Department of Sports Medicine, University Hospital Tubingen, 
      Hoppe-Seyler-Str. 6, 72076, Tubingen, Germany.
FAU - Niess, Andreas M
AU  - Niess AM
AD  - Medical Clinic, Department of Sports Medicine, University Hospital Tubingen, 
      Hoppe-Seyler-Str. 6, 72076, Tubingen, Germany.
FAU - Munz, Barbara
AU  - Munz B
AD  - Medical Clinic, Department of Sports Medicine, University Hospital Tubingen, 
      Hoppe-Seyler-Str. 6, 72076, Tubingen, Germany. barbara.munz@med.uni-tuebingen.de.
LA  - eng
PT  - Journal Article
DEP - 20180214
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (Atf3 protein, mouse)
RN  - 0 (Chemokine CXCL5)
RN  - 0 (Cxcl5 protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (Interleukin-6)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nr4a3 protein, mouse)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (interleukin-6, mouse)
RN  - 61H4T033E5 (Orotic Acid)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Activating Transcription Factor 3/biosynthesis
MH  - Animals
MH  - Chemokine CXCL5/biosynthesis
MH  - DNA-Binding Proteins/biosynthesis
MH  - Early Growth Response Protein 1/biosynthesis
MH  - Electric Stimulation
MH  - Gene Expression Regulation/drug effects
MH  - Interleukin-6/biosynthesis
MH  - Mice
MH  - Muscle Contraction/*drug effects
MH  - Myoblasts, Skeletal/cytology/*metabolism
MH  - Nerve Tissue Proteins/biosynthesis
MH  - Orotic Acid/*pharmacology
MH  - Receptors, Steroid/biosynthesis
MH  - Receptors, Thyroid Hormone/biosynthesis
MH  - TOR Serine-Threonine Kinases/biosynthesis
OTO - NOTNLM
OT  - Electrical pulse stimulation
OT  - Orotic acid
OT  - Skeletal muscle contraction
EDAT- 2018/02/16 06:00
MHDA- 2018/11/01 06:00
CRDT- 2018/02/16 06:00
PHST- 2017/10/24 00:00 [received]
PHST- 2018/02/07 00:00 [accepted]
PHST- 2018/02/16 06:00 [pubmed]
PHST- 2018/11/01 06:00 [medline]
PHST- 2018/02/16 06:00 [entrez]
AID - 10.1007/s11010-018-3330-z [pii]
AID - 10.1007/s11010-018-3330-z [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2018 Nov;448(1-2):251-263. doi: 10.1007/s11010-018-3330-z. Epub 
      2018 Feb 14.