Melatonin regulates matrix metalloproteinases after traumatic experimental spinal cord injury.
The matrix metalloproteinases (MMPs) are important enzymes that regulate developmental processes, maintain normal physiology in adulthood and have reparative roles at specific stages after an insult to the nervous system. MMPs, particularly MMP-9/gelatinase B, promote early inflammation and barrier disruption after spinal cord injury (SCI). 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 relationship between the activity of MMPs and melatonin's anti-inflammatory effects. The aim of the present study was to evaluate whether the protective effect of melatonin observed in SCI is related to the regulation of MMP-9 and MMP-2 in mice. Biochemical and zymographic methods were used to analyze MMP-9 and -2 expression and activities in spinal cord tissue from SCI-treated mice at 24 hr after the trauma. Our studies reveal that melatonin reduced SCI and lipid peroxidation in spinal cord at 24 hr after SCI. Melatonin also diminished proMMP-9 and -2 activities that were induced in the spinal cord tissues at 24 hr after SCI. The reduced activities of MMP-9 and -2 were associated with depressed expression of TNF-alpha. We propose that melatonin's ability to reduce SCI in mice is also related to a reduction in MMP-9 and MMP-2 activity and 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
D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002492:Central Nervous System Depressants; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008550:Melatonin