MMP-2 and MMP-9 are elevated in spinal cord and skin in a mouse model of ALS.
J Neurol Sci
; 294(1-2): 51-6, 2010 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-20441996
ABSTRACT
We aimed to clarify the role of matrix metalloproteinases (MMP) as a possible link between neurodegeneration and skin pathology in ALS by determination of gelatinase MMP-2 and MMP-9 in spinal cord and skin of transgenic SOD1((G93A)) mice. To elucidate mechanisms influencing MMPs, markers of oxidative damage (malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and 8-hydroxy-2'-deoxyguanosine (8OH2'dG)) as well as cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin 1ss (IL-1ss)) were determined. We measured MMP-9, MMP-2, 3-NT, TNF-alpha, and IL-1ss using ELISA, MDA using High Performance Liquid Chromatography (HPLC) and 8OH2'dG using HPLC with electrochemical detection (HPLC-ECD) in SOD1 and WT. MMP-9 was elevated in spinal cord and skin of SOD1 at 90 days (p=0.009, p<0.001) and 120 days (p<0.01, p=0.04). MMP-2 was elevated in the spinal cord at 90 days (p=0.01) and in the skin at 120 days (p=0.039). We observed a correlation of MMP-9 in spinal cord and skin of SOD1 (p=0.04). MDA was elevated in the spinal cord of SOD1 at 90 and 120 days (p=0.00006, p=0.01) and 8OH2'dG at 90 days (p=0.048). IL-1ss was elevated in the spinal cord of SOD1 at 120 days (p=0.02). Our data confirms that gelatinase MMPs are a common factor linking neurodegeneration and skin changes in ALS. It suggests that oxidative stress and microglial-derived cytokines contribute to the elevation of gelatinase MMPs especially in later stages of disease. Our data raises the question whether the skin may function as a biomarker for specific aspects of disease pathology in ALS.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Medula Espinal
/
Metaloproteinase 2 da Matriz
/
Metaloproteinase 9 da Matriz
/
Esclerose Lateral Amiotrófica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article