Acetate Reduces PGE2 Release and Modulates Phospholipase and Cyclooxygenase Levels in Neuroglia Stimulated with Lipopolysaccharide
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- 作者：Mahmoud L. Soliman (1) <br> Joyce E. Ohm (2) <br> Thad A. Rosenberger (1) <br>
- 关键词：Phospholipase ; Cyclooxygenase ; Eicosanoid ; Acetate ; Histone acetylation
- 刊名：Lipids
- 出版年：2013
- 出版时间：July 2013
- 年：2013
- 卷：48
- 期：7
- 页码：651-662
- 全文大小：704KB
- 参考文献：1. Arun P, Madhavarao CN, Moffett JR, Hamilton K, Grunberg NE, Ariyannur PS, Gahl WA, Anikster Y, Mog S, Hallows WC, Denu JM, Namboodiri AM (2010) Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease. J Inherit Metab Dis 33:195鈥?10 CrossRef <br> 2. Arun P, Ariyannur PS, Moffett JR, Xing G, Hamilton K, Grunberg NE, Ives JA, Namboodiri AM (2010) Metabolic acetate therapy for the treatment of traumatic brain injury. J Neurotrauma 27:293鈥?98 CrossRef <br> 3. Reisenauer CJ, Bhatt DP, Mitteness DJ, Slanczka ER, Gienger HM, Watt JA, Rosenberger TA (2011) Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation. J Neurochem 117:264鈥?74 CrossRef <br> 4. Brissette CA, Houdek HM, Floden AM, Rosenberger TA (2012) Acetate supplementation reduces microglia activation and brain interleukin-1尾 levels in a rat model of Lyme neuroborreliosis. J Neuroinflammation 9:249 CrossRef <br> 5. Bhatt DP, Houdek HM, Watt JA, Rosenberger TA (2013) Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis. Neurochem Int 62:296鈥?05 CrossRef <br> 6. Soliman ML, Rosenberger TA (2011) Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. Mol Cell Biochem 352:173鈥?80 CrossRef <br> 7. Soliman ML, Smith MD, Houdek HM, Rosenberger TA (2012) Acetate supplementation modulates brain histone acetylation and decreases interleukin-1beta expression in a rat model of neuroinflammation. J Neuroinflammation 9:51 CrossRef <br> 8. Soliman ML, Puig KL, Combs CK, Rosenberger TA (2012) Acetate reduces microglia inflammatory signaling in vitro. J Neurochem 123:555鈥?67 CrossRef <br> 9. Soliman ML, Combs CK, Rosenberger TA (2013) Modulation of inflammatory cytokines and mitogen-activated protein kinases by acetate in primary astrocytes. J Neuroimmune Pharmacol 8:287鈥?00 CrossRef <br> 10. Lima IV, Bastos LF, Limborco-Filho M, Fiebich BL, de Oliveira AC (2012) Role of prostaglandins in neuroinflammatory and neurodegenerative diseases. Mediators Inflamm 2012:946813 CrossRef <br> 11. Phillis JW, O鈥橰egan MH (2004) A potentially critical role of phospholipases in central nervous system ischemic, traumatic, and neurodegenerative disorders. Brain Res Brain Res Rev 44:13鈥?7 brainresrev.2003.10.002">CrossRef <br> 12. Farooqui AA, Yang HC, Rosenberger TA, Horrocks LA (1997) Phospholipase A
- 作者单位：Mahmoud L. Soliman (1) <br> Joyce E. Ohm (2) <br> Thad A. Rosenberger (1) <br><br>1. Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Room 3742, Grand Forks, ND, 58203, USA <br> 2. Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58203, USA <br>
- ISSN：1558-9307
文摘
Acetate supplementation attenuates neuroglial activation, increases histone and non-histone protein acetylation, reduces pro-inflammatory cytokine expression, and increases IL-4 transcription in rat models of neuroinflammation and Lyme鈥檚 neuroborreliosis. Because eicosanoid signaling is involved in neuroinflammation, we measured the effect acetate treatment had on phospholipase, cyclooxygenase, and prostaglandin E2b> (PGE2b>) levels in BV-2 microglia and primary astrocytes stimulated with lipopolysaccharide (LPS). In BV-2 microglia, we found that LPS increased the phosphorylation-state of cytosolic phospholipase A2b> (cPLA2b>), reduced the levels of phospholipase C (PLC) 尾1, and increased the levels of cyclooxygenase (Cox)-1 and -2. Acetate treatment returned PLC尾1 and Cox-1 levels to normal, attenuated the increase in Cox-2, but had no effect on cPLA2b> phosphorylation. In primary astrocytes, LPS increased the phosphorylation of cPLA2b> and increased the levels of Cox-1 and Cox-2. Acetate treatment in these cells reduced secretory PLA2b> IIA and PLC尾1 levels as compared to LPS-treatment groups, reversed the increase in cPLA2b> phosphorylation, and returned Cox-1 levels to normal. Acetate treatment reduced PGE2b> release in astrocytes stimulated with LPS to control levels, but did not alter PGE2b> levels in BV-2 microglia. The amount of acetylated H3K9 bound to the promoter regions of Cox-1, Cox-2, IL-1尾 and NF-魏B p65 genes, but not IL-4 in were increased in BV-2 microglia treated with acetate. These data suggest that acetate treatment can disrupt eicosanoid signaling in neuroglia that may, in part, be the result of altering gene expression due chromatin remodeling as a result of increasing H3K9 acetylation.