Melatonin reduces stress-activated/mitogen-activated protein kinases in spinal cord injury.
Permanent functional deficits following spinal cord injury (SCI) arise from both mechanical injury and from secondary tissue reactions involving inflammation. The mitogen-activated protein kinases (MAPKs) play a critical role in cell signaling and gene expression. MAPK family includes three major members: extracellular signal regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), representing three different signaling cascades. Moreover, various studies have clearly shown that high-mobility group box 1 (HMGB1) protein is implicated as a putative danger signal involved in the pathogenesis of a variety of inflammatory conditions including autoimmunity, cancer, trauma and hemorrhagic shock, and ischemia-reperfusion injury. Recently, we have reported that the pineal secretory product melatonin exerts important anti-inflammatory effects in an experimental model of SCI induced by the application of vascular clips (force of 24 g) to the dura after a four-level T5-T8 laminectomy. However, no reports are available on the effect of melatonin on MAPK signaling pathways and HMGB1 expression in SCI. The aim of the present study was to evaluate whether the melatonin protective effect observed in SCI is related to the regulation of MAPK signaling pathways and HMGB1 in mice. In this study we demonstrate the efficacy of treatment with the melatonin in SCI in mice in reducing (a) motor recovery, (b) activation of MAPKs p38, JNK and ERK1/2, (c) tumor necrosis factor-alpha expression, and (d) expression of HMGB1. We propose that melatonin's ability to reduce SCI in mice is also related to a reduction in MAPK signaling pathways and HMGB1 expression.
Esposito
Emanuela
E
Department of Experimental Pharmacology, University of Naples "Federico II", Napoli, Italy.
Genovese
Tiziana
T
Caminiti
Rocco
R
Bramanti
Placido
P
Meli
Rosaria
R
Cuzzocrea
Salvatore
S
D000704:Analysis of Variance; D000818:Animals; D024243:HMGB1 Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016472:Motor Neuron Disease / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D015599:Trauma Severity Indices; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D024243:HMGB1 Protein; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D008550:Melatonin