Details

Autor(en) / Beteiligte

• ZBINDEN-FONCEA, Hermann
• RAYMACKERS, Jean-Marc
• DELDICQUE, Louise
• RENARD, Patricia
• MARCFRANCAUX

Titel

TLR2 and TLR4 Activate p38 MAPK and JNK during Endurance Exercise in Skeletal Muscle

Ist Teil von

• Medicine and science in sports and exercise, 2012-08, Vol.44 (8), p.1463-1472

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Toll-like receptors 2 and 4 (TLR2, TLR4) are found in the membrane of skeletal muscle cells. A variety of molecular components can activate TLR2 and TLR4, among others, long-chain fatty acids. The subsequent downstream signaling triggers the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Therefore, the purpose of this study was to test whether an elevation of extracellular nonesterified fatty acids (NEFA) observed during endurance exercise may activate the MAPK and NF-κB pathways via TLR2 and TLR4. tlr2 and tlr4 mice and wild-type C57BL/6J animals (WT) were submitted to a standardized endurance exercise. Immediately after exercise, the phosphorylation state of p38 MAPK, c-Jun NH2-terminal kinase (JNK), and c-Jun was increased in the tibialis anterior (TA) and soleus (SOL) muscles of WT (P < 0.05). The phosphorylation state of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and IκB kinase α/β and the DNA-binding of NF-κB remained unchanged. The activation of p38 MAPK, JNK, and c-Jun was completely blunted in TA of tlr2 and tlr4 mice, whereas in SOL, it represented only 25% of the increase observed in WT mice. The causal relationship between NEFA concentration and MAPK activation was evaluated by injecting mice with heparin. A similar increase in plasma NEFA was observed after heparin injection than after endurance exercise. JNK and p38 MAPK were activated under heparin in TA and SOL of WT (P < 0.05) but not in muscles of tlr2 and tlr4 mice. The present study supports the idea that during endurance exercise, TLR2 and TLR4 mediate a signal linking the elevated plasma NEFA concentration to the activation of p38 MAPK and JNK.