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Differential effects of domoic acid and E. coli lipopolysaccharide on tumor necrosis factor-alpha, transforming growth factor-beta1 and matrix metalloproteinase-9 release by rat neonatal microglia: evaluation of the direct activation hypothesis.

Mayer AM, Guzman M, Peksa R, Hall M, Fay MJ, Jacobson PB, Romanic AM, Gunasekera SP - Mar Drugs (2007)

Bottom Line: LPS [3 ng/mL] but not domoic acid [1 mM] stimulated a statistically significant increase in TNF-alpha mRNA and protein generation.Furthermore, both LPS and domoic acid did not significantly affect TGF-beta1 gene expression and protein release.However, in contrast, no statistically significant increase in MMP-9 expression and release was observed after domoic acid treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, Illinois 60515, USA. amayer@midwestern.edu

ABSTRACT
The excitatory amino acid domoic acid is the causative agent of amnesic shellfish poisoning in humans. The in vitro effects of domoic acid on rat neonatal brain microglia were compared with E. coli lipopolysaccharide (LPS), a known activator of microglia mediator release over a 4 to 24 hour observation period. LPS [3 ng/mL] but not domoic acid [1 mM] stimulated a statistically significant increase in TNF-alpha mRNA and protein generation. Furthermore, both LPS and domoic acid did not significantly affect TGF-beta1 gene expression and protein release. Finally, an in vitro exposure of microglia to LPS resulted in statistically significant MMP-9 expression and release, thus extending and confirming our previous observations. However, in contrast, no statistically significant increase in MMP-9 expression and release was observed after domoic acid treatment. Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to neuronal cells, activates rat neonatal microglia and the concomitant release of the pro-inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases-9 (MMP-9), as well as the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1).

No MeSH data available.


Related in: MedlinePlus

Proton nuclear magnetic resonance spectrum of domoic acid (DOM).
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f1-md503113: Proton nuclear magnetic resonance spectrum of domoic acid (DOM).

Mentions: As shown in Figure 1, the proton NMR spectrum of the sample was consistent with the expected NMR pattern for a pure sample of domoic acid. The proton NMR spectrum showed a methyl doublet at 1.19 ppm, an olefinic methyl singlet at 1.74 ppm, three olefinic signals corresponding to the 1,1,4-trisubstituted butadiene system at 6.29 (dd), 6.06 (d) and 5.71 (dd) ppm, four methine signals at 3.91 (d), 3.76 (ddd), 3.22 (dq) and 2.98 (m) ppm, and four signals for two methylene groups at 3.64 (dd), 3.43 (dd), 2.67 (dd) and 2.43 (dd) ppm. The spectrum did not show other additional signals corresponding to any domoic acid degradation compounds. These data confirmed the presence of pure domoic acid in the sample which was analyzed and which was used in the experiments described herein.


Differential effects of domoic acid and E. coli lipopolysaccharide on tumor necrosis factor-alpha, transforming growth factor-beta1 and matrix metalloproteinase-9 release by rat neonatal microglia: evaluation of the direct activation hypothesis.

Mayer AM, Guzman M, Peksa R, Hall M, Fay MJ, Jacobson PB, Romanic AM, Gunasekera SP - Mar Drugs (2007)

Proton nuclear magnetic resonance spectrum of domoic acid (DOM).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2367328&req=5

f1-md503113: Proton nuclear magnetic resonance spectrum of domoic acid (DOM).
Mentions: As shown in Figure 1, the proton NMR spectrum of the sample was consistent with the expected NMR pattern for a pure sample of domoic acid. The proton NMR spectrum showed a methyl doublet at 1.19 ppm, an olefinic methyl singlet at 1.74 ppm, three olefinic signals corresponding to the 1,1,4-trisubstituted butadiene system at 6.29 (dd), 6.06 (d) and 5.71 (dd) ppm, four methine signals at 3.91 (d), 3.76 (ddd), 3.22 (dq) and 2.98 (m) ppm, and four signals for two methylene groups at 3.64 (dd), 3.43 (dd), 2.67 (dd) and 2.43 (dd) ppm. The spectrum did not show other additional signals corresponding to any domoic acid degradation compounds. These data confirmed the presence of pure domoic acid in the sample which was analyzed and which was used in the experiments described herein.

Bottom Line: LPS [3 ng/mL] but not domoic acid [1 mM] stimulated a statistically significant increase in TNF-alpha mRNA and protein generation.Furthermore, both LPS and domoic acid did not significantly affect TGF-beta1 gene expression and protein release.However, in contrast, no statistically significant increase in MMP-9 expression and release was observed after domoic acid treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, Illinois 60515, USA. amayer@midwestern.edu

ABSTRACT
The excitatory amino acid domoic acid is the causative agent of amnesic shellfish poisoning in humans. The in vitro effects of domoic acid on rat neonatal brain microglia were compared with E. coli lipopolysaccharide (LPS), a known activator of microglia mediator release over a 4 to 24 hour observation period. LPS [3 ng/mL] but not domoic acid [1 mM] stimulated a statistically significant increase in TNF-alpha mRNA and protein generation. Furthermore, both LPS and domoic acid did not significantly affect TGF-beta1 gene expression and protein release. Finally, an in vitro exposure of microglia to LPS resulted in statistically significant MMP-9 expression and release, thus extending and confirming our previous observations. However, in contrast, no statistically significant increase in MMP-9 expression and release was observed after domoic acid treatment. Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to neuronal cells, activates rat neonatal microglia and the concomitant release of the pro-inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases-9 (MMP-9), as well as the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1).

No MeSH data available.


Related in: MedlinePlus