Minocycline Effects on the Cerebrospinal Fluid Proteome of Experimental Autoimmune Encephalomyelitis Rats
| Autor: | Lennard J. M. Dekker, Hans van Aken, Tinka Tuinstra, Amos Attali, Ernst Suidgeest, Therese Rosenling, Rogier Q. Hintzen, Theo M. Luider, Christoph Stingl, Alain J. van Gool, Marcel P. Stoop, Roland J. W. Meesters, Rainer Bischoff |
|---|---|
| Přispěvatelé: | Neurology, Psychiatry, Analytical Biochemistry, Groningen Research Institute of Pharmacy, Medicinal Chemistry and Bioanalysis (MCB) |
| Rok vydání: | 2012 |
| Předmět: |
Male
EXPRESSION Encephalomyelitis Autoimmune Experimental Proteome MATRIX METALLOPROTEINASE-2 PROTEINS Freund's Adjuvant experimental autoimmune encephalomyelitis Proteomics multiple sclerosis EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS Biochemistry cerebrospinal fluid DISEASE SERUM Cerebrospinal fluid proteomics minocycline Adjuvants Immunologic Tandem Mass Spectrometry medicine Animals IDENTIFICATION business.industry EAE Multiple sclerosis Experimental autoimmune encephalomyelitis Cerebrospinal Fluid Proteins General Chemistry Minocycline Complement C3 medicine.disease Carboxypeptidase B Rats Neuroprotective Agents Mitochondrial medicine [IGMD 8] Mechanism of action REMITTING MULTIPLE-SCLEROSIS Rats Inbred Lew selected reaction monitoring Immunology medicine.symptom SPINAL-CORD business Carboxypeptidase B2 medicine.drug |
| Zdroj: | Journal of Proteome Research, 11(8), 4315-4325. American Chemical Society Journal of Proteome Research, 11, 8, pp. 4315-25 Journal of Proteome Research, 11, 4315-25 Journal of Proteome Research, 11(8), 4315-4325. NLM (Medline) |
| ISSN: | 1535-3893 |
| Popis: | Item does not contain fulltext To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of neurological symptoms, and proteomics analysis was performed using nano-LC-Orbitrap mass spectrometry. Additionally, the minocycline concentration in CSF was determined using quantitative matrix-assisted laser desorption/ionization-triple-quadrupole tandem mass spectrometry (MALDI-MS/MS) in the selected reaction monitoring (SRM) mode. Fifty percent of the minocycline-treated EAE animals did not show neurological symptoms on day 14 ("responders"), while the other half displayed neurological symptoms ("nonresponders"), indicating that minocycline delayed disease onset and attenuated disease severity in some, but not all, animals. Neither CSF nor plasma minocycline concentrations correlated with the onset of symptoms or disease severity. Analysis of the proteomics data resulted in a list of 20 differentially abundant proteins between the untreated animals and the responder group of animals. Two of these proteins, complement C3 and carboxypeptidase B2, were validated by quantitative LC-MS/MS in the SRM mode. Differences in the CSF proteome between untreated EAE animals and minocycline-treated responders were similar to the differences between minocycline-treated responders and nonresponders (70% overlap). Six proteins that remained unchanged in the minocycline-treated animals but were elevated in untreated EAE animals may be related to the mechanism of action of minocycline. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|