Independent regulation of cyclo-oxygenase 2 expression by p42/44 mitogen-activated protein kinases and Ca2+/calmodulin-dependent kinase

Goppelt‐Struebe, Margarete; Hahn, Angelika F.; STROEBEL, Martin; REISER, Christian O.A.

doi:10.1042/0264-6021:3390329

Cited by 17 publications

(4 citation statements)

References 12 publications

(24 reference statements)

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“…2C). The used concentration of PD98059 (10 M) was shown earlier to prevent activation of ERK 1/2 in mesangial cells (18). Furthermore, inhibition of phosphatidylinositol-3 kinase (PI-3 kinase) by LY294002 or inhibition of Src family kinases by PP2 significantly reduced the upregulation of TSP-1 expression by ϳ50% (Fig.…”

Section: Resultsmentioning

confidence: 87%

The small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression

Giehl

Graneß²,

Goppelt‐Struebe³

2008

American Journal of Physiology-Renal Physiology

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Thrombospondin-1 (TSP-1), which is synthesized by mesangial cells, is known for its anti-angiogenic activity and its ability to activate latent TGF-beta. TSP-1 is upregulated in renal diseases associated with tissue remodeling. Therefore, we hypothesized that the expression of TSP-1 might be modulated by changes in cell morphology involving proteins of the Rho family. Spreading of mesangial cells after detachment and reseeding was characterized by the formation of lamellipodia and focal adhesions, pointing toward a Rac-1-mediated rearrangement of actin structures. Clustering of focal adhesion proteins was also observed in a model system of nocodazole-induced disruption of microtubules. These morphological alterations were impeded by pharmacological inhibition of Src family kinases, of the small GTPase Rac-1, or by downregulation of Rac-1 by siRNA. Upon cell spreading, TSP-1 was upregulated in the absence and much more prominently in the presence of serum, but also after nocodazole treatment. TSP-1 upregulation was controlled by activation of Src family kinases, ERK 1/2 and Rac-1, whereas activation of RhoA-ROCK signaling was not linked to TSP-1 induction. We thus provide evidence that TSP-1 expression is induced by common signaling pathways, which are activated by morphological alterations of renal mesangial cells or by soluble factors as contained in serum, and these pathways include Src family kinases, ERK 1/2 and Rac-1. Our data suggest that tissue remodeling activates gene expression of pathophysiologically relevant proteins such as TSP-1.

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Section: Resultsmentioning

confidence: 87%

The small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression

Giehl

Graneß²,

Goppelt‐Struebe³

2008

American Journal of Physiology-Renal Physiology

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“…5-Methylenetetrahydrofolate deficiency may lead to increased cellular homocysteine, which could cause nerve injury, inflammation, and liver cell damage, or even induce cell toxicity and cancer [18]. In addition, 5-methylenetetrahydrofolate is involved in the synthesis of 5-hydroxytryptamine (5-HT, serotonin), which is a potent inducer of the early-response gene cyclooxygenase 2 (Cox-2) [19], thereby increasing the inflammatory response in rats. As revealed by the metabolomic fingerprinting analysis in the present study, the serum levels of choline and 5-methylenetetrahydrofolate in the RPR and RPA groups had the tendency to recover to normal levels, although these values were still relatively lower than those of the VEH group.…”

Section: Resultsmentioning

confidence: 99%

Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-Induced Acute Liver Injury: An Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) Based Metabolomic Approach for the Pharmacodynamic Study of Traditional Chinese Medicines (TCMs)

Wang

Xiong

Teng

et al. 2012

IJMS

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Metabolomics has been frequently used in pharmacodynamic studies, especially those on traditional Chinese medicine (TCM). Radix Paeoniae Alba and Radix Paeoniae Rubra are popularly used in TCM, and both have hepatoprotective effects. In this study, a CCl4-induced acute liver injury rat model was established and confirmed by the observed serum aminotransferase activities. The metabolomics approach was applied to study the influence of Radix Paeoniae Alba and Radix Paeoniae Rubra on the metabolic changes in rats with acute liver injury. The partial least-squares-discriminant analysis (PLS-DA) of rat serum and their ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) fingerprints allowed discrimination of controlled, acute liver injury-model rats after administration of the two types of TCMs. The time-dependent PLS-DA plots showed that the changes in the metabolic patterns of the rats, which were administered with the TCMs, had stabilized within 2 h after they received the intraperitoneal CCl4 injection. The results indicated the protective effect of TCMs against liver injury. Several potential biomarkers were detected and identified, which included creatine, deoxycholic acid, choline, 5-methylenetetrahydrofolate, folic acid, and glycocholic acid. The physiological significance of these metabolic changes was discussed.

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“…The 5-HT 2A receptor activates PLC-β leading to the accumulation of inositol phosphates and elevations of intracellular Ca 2+ in many tissues and cell types ( 17 , 21 ). It also has the capability to increase Cyclo-oxygenase-2 (COX-2) activity and the release of transforming growth factor beta (TGF-β) via the stimulation of ERK MAPK activity ( 22 , 23 ). Furthermore, ligated 5-HT 2A was shown to interact with the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) pathway controlling a rapid tyrosine phosphorylation of Jak2 and STAT3 that leads to the nuclear translocation of STAT3 ( 24 ).…”

Section: Molecular Basics Of Serotonin and Sigma Receptor Signalingmentioning

confidence: 99%

Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

Szabó

2015

Front. Immunol.

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Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine, and 3,4-methylenedioxy-methamphetamine will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer’s disease.

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Independent regulation of cyclo-oxygenase 2 expression by p42/44 mitogen-activated protein kinases and Ca2+/calmodulin-dependent kinase

Cited by 17 publications

References 12 publications

The small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression

The small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression

Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-Induced Acute Liver Injury: An Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) Based Metabolomic Approach for the Pharmacodynamic Study of Traditional Chinese Medicines (TCMs)

Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

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