Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2

Kim, Eun Joo; Kwon, Kyoung Ja; Park, Jee Young; Lee, Soo Hwan; Moon, Chang Hyun; Baik, Eun Joo

doi:10.1016/s0006-8993(02)02480-0

Cited by 132 publications

(65 citation statements)

References 38 publications

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“…2, C and D, pre-treatment with CD-101 at various concentrations (0.1, 1, and 2.5 μM) significantly inhibited LPS-induced iNOS protein and mRNA expression in a dose-dependent manner. COX-2 is another important inflammatory enzyme that is upregulated by cytokines, endotoxins, and various neurodegenerative diseases (30). Therefore, we investigated the effects of CD-101 on COX-2 in LPS-activated BV-2 microglial cells.…”

Section: Effect Of Cd-101 On Lps-stimulated Inos and Cox-2 Mrna Protmentioning

confidence: 99%

Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells

Park

Kim

et al. 2013

J Pharmacol Sci

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Abstract. Microglial-mediated neuroinflammation has recently been implicated as one of the important mechanisms responsible for the progression of neurodegenerative diseases. Activated microglia cells produce various neurotoxic factors that are harmful to neurons. Therefore, suppression of the inflammatory response elicited by activated microglia is considered a potential therapeutic target for neurodegenerative diseases. The cannabinoid (CB) system is widespread in the central nervous system and is very crucial for modulating a spectrum of neurophysiological functions such as pain, appetite, and cognition. In the present study, we synthesized and investigated a novel CB derivative (CD-101) for its ability to suppress lipopolysaccharide (LPS)-mediated activation of BV-2 microglial cells and subsequent release of various inflammatory mediators. CD-101 significantly inhibited the production of inflammatory markers such as nitric oxide, cyclooxygenase-2, and pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. The anti-neuroinflammatory effect of this novel cannabinoid derivative occurred by inhibiting p38MAPK phosphorylation and by decreasing nuclear translocation of p65 subunit of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells. These results suggest that the use of the cannabinoid derivative CD-101 might be a potential therapeutic target against neuroinflammatory disorders.

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Section: Effect Of Cd-101 On Lps-stimulated Inos and Cox-2 Mrna Protmentioning

confidence: 99%

Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells

Park

Kim

et al. 2013

J Pharmacol Sci

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“…For mixed cortical neuron/astrocyte cell cultures, first, astrocytes were prepared from neonatal rat as described previously (Kim et al, 2002). Sprague-Dawley neonatal (1 to 2 days old) rats were anesthetized by intraperitoneal injection of ketamine (1.0 mg/pup).…”

Section: Preparation Of Mixed Cortical Neuron/astrocyte Cell Culturesmentioning

confidence: 99%

Preconditioning Mediated by Sublethal Oxygen—Glucose Deprivation-Induced Cyclooxygenase-2 Expression via the Signal Transducers and Activators of Transcription 3 Phosphorylation

Kim

Raval

Pérez-Pinzón

2008

J Cereb Blood Flow Metab

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The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (ePKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen-glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or ePKC activation. Inhibition of either ePKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after ePKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance.

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“…Products of activated microglia including NO, TNF-α, and reactive oxygen species may contribute to the loss of neurons in these diseases. A variety of PPAR-γ agonists have been demonstrated to indirectly protect neurons in neuron-glial co-cultures by inhibiting glial cell activation [9,28]. PPAR-γ agonists also directly protect cerebellar granule neurons [21,48].…”

Section: Ppar-γ: Effects On Neuronal Cell Viabilitymentioning

confidence: 99%

Hormone regulation of microglial cell activation: relevance to multiple sclerosis

Drew

Storer

et al. 2005

Brain Research Reviews

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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of proteins. The role of PPARs in regulating the transcription of genes involved in glucose and lipid metabolism has been extensively characterized. Interestingly, PPARs have also been demonstrated to mediate inflammatory responses.Microglia participate in pathology associated with multiple sclerosis (MS). Upon activation, microglia produce molecules including NO and TNF-α that can be toxic to CNS cells including myelin-producing oligodendrocytes and neurons, which are compromised in the course of MS.Previously, we and others demonstrated that PPAR-γ agonists including 15d-PGJ 2 are effective in the treatment of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. PPAR-γ modulation of EAE may occur, at least in part, by inhibition of microglial cell activation. Here, we indicate that 15d-PGJ 2 is a more potent inhibitor of microglial activation than thiazolidinediones, which are currently used to treat diabetes. Furthermore, 15d-PGJ 2 acts cooperatively with 9-cis retinoic acid, the ligand for the retinoid X receptor (RXR), in inhibiting microglial cell activation. This suggests that 15d-PGJ 2 and 9-cis RA inhibit cell activation through the formation of PPAR-γ/ RXR heterodimers. Interestingly, PGA 2 , which like 15d-PGJ 2 is a cyclopentenone prostaglandin, but which unlike 15d-PGJ 2 does not bind PPAR-γ, is a potent inhibitor of microglial cell activation. Collectively, these studies suggest that 15d-PGJ 2 inhibits microglial cell activation by PPAR-γ-dependent as well as PPAR-γ-independent mechanisms. The studies further suggest that the PPAR-γ agonist 15d-PGJ 2 in combination with retinoids may be effective in the treatment of MS.

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Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2

Cited by 132 publications

References 38 publications

Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells

Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells

Preconditioning Mediated by Sublethal Oxygen—Glucose Deprivation-Induced Cyclooxygenase-2 Expression via the Signal Transducers and Activators of Transcription 3 Phosphorylation

Hormone regulation of microglial cell activation: relevance to multiple sclerosis

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