Neuronal prostaglandin endoperoxide synthase 2 responses to oxygen and glucose deprivation are mediated by mitogen-activated protein kinase ERK1/2

2005 ◽  
Vol 1060 (1-2) ◽  
pp. 100-107 ◽  
Author(s):  
Daying Zhang ◽  
Charles E. Wood
Keyword(s):  
Protein Kinase ◽  
Glucose Deprivation ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen And Glucose Deprivation ◽  
Prostaglandin Endoperoxide ◽  
Mitogen Activated Protein ◽  
Prostaglandin Endoperoxide Synthase

scholarly journals Induction of prostaglandin endoperoxide synthase 2 by mitogen-activated protein kinase cascades

2000 ◽  
Vol 352 (2) ◽  
pp. 419 ◽  
Author(s):  
Ann McGINTY ◽  
Marco FOSCHI ◽  
Yu-Wen E. CHANG ◽  
Jiahuai HAN ◽  
Michael J. DUNN ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Prostaglandin Endoperoxide ◽  
Mitogen Activated Protein ◽  
Prostaglandin Endoperoxide Synthase

scholarly journals Induction of prostaglandin endoperoxide synthase 2 by mitogen-activated protein kinase cascades

2000 ◽  
Vol 352 (2) ◽  
pp. 419-424 ◽  
Author(s):  
Ann MCGINTY ◽  
Marco FOSCHI ◽  
Yu-Wen E. CHANG ◽  
Jiahuai HAN ◽  
Michael J. DUNN ◽  
...  
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Inflammatory Diseases ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Diverse Range ◽  
Adenoviral Infection ◽  
Prostaglandin Endoperoxide ◽  
Mitogen Activated Protein ◽  
Prostaglandin Endoperoxide Synthase

Prostaglandin endoperoxide synthase (PGHS) catalyses the rate-limiting step in the formation of prostaglandin and thromboxane eicosanoids from arachidonic acid released by phospholipase A2. Two forms of PGHS exist, PGHS-1 and PGHS-2. PGHS-2, normally absent from cells, is rapidly expressed in response to a wide variety of stimuli and has been implicated in the pathogenesis of colon cancer and several inflammatory diseases. The three principal mitogen-activated protein kinase (MAPK) pathways are the extracellular signal-regulated protein kinase (ERK), the c-Jun N-terminal kinase (JNK) cascade and the p38-MAPK cascade. The present study was undertaken to investigate the putative involvement of the MAPK cascades in PGHS-2 induction. The potential role of ERK in PGHS-2 up-regulation was assessed by using cell lines expressing, both stably and after adenoviral infection, constitutively active forms of its upstream activator MAPK/ERK kinase (MEK1). The possible involvement of JNK and p38-MAPK in positively modulating PGHS-2 transcription was investigated by using adenovirus-mediated transfer of active forms of their respective specific upstream kinases, mitogen-activated protein kinase kinase (MKK) 7 and MKK3/MKK6. ERK activation promoted the induction of PGHS-2 mRNA and protein. Similarly, activation of JNK by Ad-MKK7D and p38-MAPK by Ad-MKK3bE/Ad-MKK6bE resulted in the increased expression of PGHS-2. These results provide evidence that activation of all three of the major mammalian MAPK leads to the induction of PGHS-2 mRNA and protein. Because PGHS-2 is up-regulated by a diverse range of stimuli, both mitogenic and stress-evoking, these results provide evidence that the convergence point of these stimuli could be the activation of one or more MAPK cascade(s).

Isoflurane Preconditions Hippocampal Neurons against Oxygen–Glucose Deprivation

2005 ◽  
Vol 103 (3) ◽  
pp. 532-539 ◽  
Author(s):  
Philip E. Bickler ◽  
Xinhua Zhan ◽  
Christian S. Fahlman
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Hippocampal Slice ◽  
Binding Protein ◽  
Glucose Deprivation ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Glucose Deprivation ◽  
Hippocampal Slice Cultures ◽  
Mitogen Activated Protein ◽  
Associated Proteins

Background Isoflurane preconditions neurons to improve tolerance of subsequent ischemia in both intact animal models and in in vitro preparations. The mechanisms for this protection remain largely undefined. Because isoflurane increases intracellular Ca2+ concentrations and Ca2+ is involved in many processes related to preconditioning, the authors hypothesized that isoflurane preconditions neurons via Ca2+-dependent processes involving the Ca2+- binding protein calmodulin and the mitogen-activated protein kinase-ERK pathway. Methods The authors used a preconditioning model in which organotypic cultures of rat hippocampus were exposed to 0.5-1.5% isoflurane for a 2-h period 24 h before an ischemia-like injury of oxygen-glucose deprivation. Survival of CA1, CA3, and dentate neurons was assessed 48 later, along with interval measurements of intracellular Ca2+ concentration (fura-2 fluorescence microscopy in CA1 neurons), mitogen-activated protein kinase p42/44, and the survival associated proteins Akt and GSK-3beta (in situ immunostaining and Western blots). Results Preconditioning with 0.5-1.5% isoflurane decreased neuron death in CA1 and CA3 regions of hippocampal slice cultures after oxygen-glucose deprivation. The preconditioning period was associated with an increase in basal intracellular Ca2+ concentration of 7-15%, which involved Ca2+ release from inositol triphosphate-sensitive stores in the endoplasmic reticulum, and transient phosphorylation of mitogen-activated protein kinase p42/44 and the survival-associated proteins Akt and GSK-3beta. Preconditioning protection was eliminated by the mitogen-activated extracellular kinase inhibitor U0126, which prevented phosphorylation of p44 during preconditioning, and by calmidazolium, which antagonizes the effects of Ca2+-bound calmodulin. Conclusions Isoflurane, at clinical concentrations, preconditions neurons in hippocampal slice cultures by mechanisms that apparently involve release of Ca2+ from the endoplasmic reticulum, transient increases in intracellular Ca2+ concentration, the Ca2+ binding protein calmodulin, and phosphorylation of the mitogen-activated protein kinase p42/44.

scholarly journals Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F2α production in hamster Leydig cells

Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 163-175 ◽  
Author(s):  
María E Matzkin ◽  
Silvia I Gonzalez-Calvar ◽  
Artur Mayerhofer ◽  
Ricardo S Calandra ◽  
Mónica B Frungieri
Keyword(s):  
Sexual Development ◽  
Leydig Cells ◽  
Prostaglandin F2α ◽  
Mitogen Activated Protein Kinase ◽  
Prostaglandin Endoperoxide ◽  
Mitogen Activated Protein ◽  
Key Enzyme ◽  
Prostaglandin Endoperoxide Synthase ◽  
Regulatory Loop

We have previously observed expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the key enzyme in the biosynthesis of prostaglandins (PGs), in reproductively active Syrian hamster Leydig cells, and reported an inhibitory role of PGF2α on hamster testicular steroidogenesis. In this study, we further investigated PTGS2 expression in hamster Leydig cells during sexual development and photoperiodic gonadal regression. Since PTGS2 is mostly expressed in pubertal and reproductively active adult hamsters with high circulating levels of LH and androgens, we studied the role of these hormones in the regulation/maintenance of testicular PTGS2/PGF2α. In active hamster Leydig cells, LH/hCG and testosterone induced PTGS2 and PGF2α production, and their actions were abolished by the antiandrogen bicalutamide (Bi). These results indicate that LH does not exert a direct effect on PG synthesis. Testosterone also stimulated phosphorylation of the mitogen-activated protein kinase isoforms 3/1 (MAPK3/1) within minutes and hours, but the testosterone metabolite dihydrotestosterone had no effect on PTGS2 and MAPK3/1. Because Bi and U0126, an inhibitor of the MAP kinase kinases 1 and 2 (MAP2K1/2), abolished testosterone actions on MAPK3/1 and PTGS2, our studies suggest that testosterone directly induces PTGS2/PGF2α in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves MAPK3/1 activation. Since PGF2α inhibits testosterone production, it might imply the existence of a regulatory loop that is setting a brake on steroidogenesis. Thus, the androgen environment might be crucial for the regulation of testicular PG production at least during sexual development and photoperiodic variations in hamsters.

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