Docosahexaenoic Acid Enhances Cyclooxygenase-2 Induction by Facilitating p44/42, but Not p38, Mitogen-Activated Protein Kinase Activation in Rat Vascular Smooth Muscle Cells

Machida, Takuji; Hiramatsu, Miho; Hamaue, Naoya; Minami, Masaru; Hirafuji, Masahiko

doi:10.1254/jphs.sc0050099

Cited by 19 publications

(17 citation statements)

References 15 publications

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“…NOS protein expression and ERK activation were evaluated by Western blot analysis as described previously (Hirafuji et al, 2002;Machida et al, 2005). The blot was incubated for 2 h with anti-iNOS, anti-endothelial NOS (eNOS), anti-neuronal NOS (nNOS) antibody, and antibodies against phosphorylated and total ERK.…”

Section: Methodsmentioning

confidence: 99%

Sphingosine 1-Phosphate Inhibits Nitric Oxide Production Induced by Interleukin-1β in Rat Vascular Smooth Muscle Cells

Machida¹,

Hamaya²,

Izumi³

et al. 2008

J Pharmacol Exp Ther

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Sphingosine 1-phosphate (S1P) is a lipid mediator that exerts potent and diverse biological effects on several cardiovascular cells. We investigated the effect of S1P on interleukin (IL)-1␤-induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression in rat vascular smooth muscle cells (VSMCs). S1P inhibited NO production at concentrations higher than 0.1 M; this was associated with the inhibition of iNOS protein and mRNA expression. S1P also inhibited IL-1␤-induced GTP cyclohydrolase I (GTPCH) mRNA expression. Pertussis toxin (PTX) partially attenuated the inhibitory effects of S1P on NO production and iNOS protein induction, whereas it completely blocked the inhibitory effects on iNOS and GTPCH mRNA expression. S1P inhibited iNOS expression in Ca . S1P significantly inhibited IL-1␤-induced persistent activation of extracellular signal-regulated kinase (ERK) but had no effect in Ca 2ϩ -depleted conditions. Thus, S1P inhibits IL-1␤ induction of NO production and iNOS expression in rat VSMCs through multiple mechanisms involving both PTX-sensitive and -insensitive G proteins coupled to S1P receptors. Furthermore, Ca 2ϩ

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Section: Methodsmentioning

confidence: 99%

Sphingosine 1-Phosphate Inhibits Nitric Oxide Production Induced by Interleukin-1β in Rat Vascular Smooth Muscle Cells

Machida¹,

Hamaya²,

Izumi³

et al. 2008

J Pharmacol Exp Ther

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“…The fatty acids influence the fluidity of the neuronal plasma membrane as well as the functional properties of integral membrane protein (1). Docosahexaenoic acid (DHA, C22:6) is a dietary essential omega-3 fatty acid and is one of the major components of membrane phospholipids in the mammalian nervous system (1,2). The omega-3 fatty acids possess both cardio-and neuro-protective properties that have been documented in animal studies (3,4).…”

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confidence: 99%

Modulation of ATP-Induced Inward Currents by Docosahexaenoic Acid and Other Fatty Acids in Rat Nodose Ganglion Neurons

et al. 2006

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Abstract. The effects of docosahexaenoic acid (DHA) and other fatty acids on P2X-receptormediated inward currents in rat nodose ganglion neurons were studied using the nystatin perforated patch-clamp technique. DHA accelerated the desensitization rate of the ATP-induced current. DHA showed use-dependent inhibition of the peak ATP-induced current. Other polyunsaturated fatty acids, such as arachidonic acid and eicosapentaenoic acid, displayed a similar use-dependent inhibition. The inhibitory effects of saturated fatty acids including palmitic acid and arachidic acid were weaker than those of polyunsaturated fatty acids. The results suggest that fatty acids may modulate the P2X receptor-mediated response when the channel is in the openstate.

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“…In contrast with the downregulation of gene expression by DHA, some studies showed an upregulatory effect of DHA on gene expression. DHA slightly enhanced both IL-1b and phorbol 12-myristate 13-acetate-induced COX-2 expression in rat vascular smooth muscle cells [39]. Also, IL-1b and phorbol 12-myristate 13-acetate induced both rapid and prolonged activation of p44/42 MAPK, but not p38 MAPK, was stimulated by DHA.…”

Section: Discussionmentioning

confidence: 79%

Docosahexaenoic acid downregulates phenobarbital‐induced cytochrome P450 2B1 gene expression in rat primary hepatocytes via the c‐Jun NH2‐terminal kinase mitogen‐activated protein kinase pathway

Liu

et al. 2009

Molecular Nutrition Food Res

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Mitogen-activated protein kinase (MAPK) pathways play central roles in the transduction of extracellular stimuli into cells and the regulation of expression of numerous genes. Docosahexaenoic acid (DHA) was shown to be involved in the regulation of expression of drug metabolizing enzymes (DMEs) in rat primary hepatocytes in response to xenobiotics. Cytochrome P450 2B1 (CYP 2B1) is a DME that is dramatically induced by phenobarbital-type inducers. The constitutive androstane receptor (CAR) plays a critical role in regulating the expression of DMEs, and the phosphorylation/dephosphorylation of CAR is an important event in CYP 2B1 expression. In the present study, we determined the effect of DHA on MAPK transactivation and its role in CYP 2B1 expression induced by phenobarbital. c-Jun NH2-terminal kinase (JNK) JNK1/2 and ERK1/2 were activated by phenobarbital in a dose-dependent manner. DHA (100 muM) inhibited JNK1/2 and ERK2 activation induced by phenobarbital in a time-dependent manner. Both SP600125 (a JNK inhibitor) and SB203580 (a p38 MAPK inhibitor) inhibited CYP 2B1 protein and mRNA expression induced by phenobarbital. SB203580 significantly increased the intracellular 3'-5'-cyclic adenosine monophosphate (cAMP) concentration compared with a control group (p < 0.05). Our results suggest that inhibition of JNK activation by DHA is at least part of the mechanisms of DHA's downregulation of CYP 2B1 expression induced by phenobarbital.

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Docosahexaenoic Acid Enhances Cyclooxygenase-2 Induction by Facilitating p44/42, but Not p38, Mitogen-Activated Protein Kinase Activation in Rat Vascular Smooth Muscle Cells

Cited by 19 publications

References 15 publications

Sphingosine 1-Phosphate Inhibits Nitric Oxide Production Induced by Interleukin-1β in Rat Vascular Smooth Muscle Cells

Sphingosine 1-Phosphate Inhibits Nitric Oxide Production Induced by Interleukin-1β in Rat Vascular Smooth Muscle Cells

Modulation of ATP-Induced Inward Currents by Docosahexaenoic Acid and Other Fatty Acids in Rat Nodose Ganglion Neurons

Docosahexaenoic acid downregulates phenobarbital‐induced cytochrome P450 2B1 gene expression in rat primary hepatocytes via the c‐Jun NH2‐terminal kinase mitogen‐activated protein kinase pathway

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