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Peter M. Zygmunt Anna Ermund Pouya Movahed David A. Andersson Charlotte Simonsen Bo A. G. J?nsson Anders Blomgren Bryndis Birnir Stuart Bevan Alain Eschalier Christophe Mallet Ana Gomis Edward D. H?gest?tt 《PloS one》2013,8(12)
Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which can regulate TRPV1 activity via different mechanisms. Here we explored the possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1-arachidonoylglycerol, and not metabolites of these monoacylglycerols, activate TRPV1 and contribute to this signaling cascade. 2-Arachidonoylglycerol and 1-arachidonoylglycerol activated native TRPV1 on vascular sensory nerve fibers and heterologously expressed TRPV1 in whole cells and inside-out membrane patches. The monoacylglycerol lipase inhibitors methylarachidonoyl-fluorophosphonate and JZL184 prevented the metabolism of deuterium-labeled 2-arachidonoylglycerol and deuterium-labeled 1-arachidonoylglycerol in arterial homogenates, and enhanced TRPV1-mediated vasodilator responses to both monoacylglycerols. In mesenteric arteries from TRPV1 knock-out mice, vasodilator responses to 2-arachidonoylglycerol were minor. Bradykinin and adenosine triphosphate, ligands of phospholipase C-coupled membrane receptors, increased the content of 2-arachidonoylglycerol in dorsal root ganglia. In HEK293 cells expressing the phospholipase C-coupled histamine H1 receptor, exposure to histamine stimulated the formation of 2-AG, and this effect was augmented in the presence of JZL184. These effects were prevented by the diacylglycerol lipase inhibitor tetrahydrolipstatin. Histamine induced large whole cell currents in HEK293 cells co-expressing TRPV1 and the histamine H1 receptor, and the TRPV1 antagonist capsazepine abolished these currents. JZL184 increased the histamine-induced currents and tetrahydrolipstatin prevented this effect. The calcineurin inhibitor ciclosporin and the endogenous “entourage” compound palmitoylethanolamide potentiated the vasodilator response to 2-arachidonoylglycerol, disclosing TRPV1 activation of this monoacylglycerol at nanomolar concentrations. Furthermore, intracerebroventricular injection of JZL184 produced TRPV1-dependent antinociception in the mouse formalin test. Our results show that intact 2-arachidonoylglycerol and 1-arachidonoylglycerol are endogenous TRPV1 activators, contributing to phospholipase C-dependent TRPV1 channel activation and TRPV1-mediated antinociceptive signaling in the brain. 相似文献
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Rafał Krętowski Anna Stypułkowska Marzanna Cechowska-Pasko 《Molecular and cellular biochemistry》2015,398(1-2):165-173
The inhibition of the 26S proteasome evokes endoplasmic reticulum stress, which has been shown to be implicated in the antitumoral effects of proteasome inhibitors. The cellular and molecular effects of the proteasome inhibitor—bortezomib—on human colon cancer cells are as yet poorly characterized. Bortezomib selectively induces apoptosis in some cancer cells. However, the nature of its selectivity remains unknown. Previously, we demonstrated that, in contrast to normal fibroblasts, bortezomib treatment evoked strong effect on apoptosis of breast cancer cells incubated in hypoxic and normoxic conditions. The study presented here provides novel information on the cellular effects of bortezomib in DLD-1 colon cancer cells line. We observe twofold higher percentage of apoptotic cells incubated for 48 h with 25 and 50 nmol/l of bortezomib in hypoxic conditions and four-, fivefold increase in normoxic conditions in comparison to control cells, incubated without bortezomib. It is of interest that bortezomib evokes strong effect on necrosis of DLD-1 colon cancer cell line. We observe the sixfold increase in necrosis of DLD-1 cells incubated with 25 or 50 nmol/l of bortezomib for 48 h in hypoxia and fourfold increase in normoxic conditions in comparison to adequate controls. We suggest that bortezomib may be candidates for further evaluation as chemotherapeutic agents for human colon cancer. 相似文献
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Anna V. Klenova 《PloS one》2015,10(11)
Begging behaviour is an important element in the parent-offspring conflict; it has been studied in many avian species. However, the majority of the studies have been entirely based on the call counts, and they agreed that vocal activity was a good indicator of chick’s nutritional need and/or condition. Fewer researches were dedicated to the temporal-frequency variables of the begging calls themselves and they showed contrary results. Here begging behaviour in three burrow nested, uniparous species of auks (Alcidae) was studied. These objects provide an opportunity to study the signalling value of begging calls in the absence of important confounding factors such as nestling competition and predation pressure. I recorded calls of individual chicks in two conditions: during natural feeding and after experimental four-hour food deprivation. I found that almost all measured acoustic variables contain information about the chick’s state in all studied species. The hungry chicks produced calls higher in fundamental frequency and power variables and at higher calling rate compared to naturally feeding chicks. The effect of food deprivation on most acoustic variables exceeded both the effects of individuality and species. In all studied species, the frequency variables were stronger affected by hunger than the calling rate and call durations. I suppose that such strong change of acoustic variables after food deprivation can be explained by absence of vocal individual identification in these birds. As parents do not need to check individuality of the chick in the burrow, which they find visually during the day time, the chicks could use all of the acoustic variables to communicate about their nutritional needs. 相似文献
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Anna Sterniczuk Elbieta I. Waajtys-Rode Anna B. Wojtczak 《Cell biochemistry and function》1991,9(1):13-21
The flux through branched-chain alpha-ketoacid dehydrogenase and the activity of the branched-chain alpha-ketoacid dehydrogenase complex were measured in hepatocytes isolated from fed, starved and alloxan diabetic rats. The highest rate of branched-chain alpha-ketoacid oxidation was found in hepatocytes isolated from starved rats, slightly lower in those from fed rats, and significantly lower in diabetic hepatocytes. The amount of the active form of branched-chain alpha-ketoacid dehydrogenase was only slightly diminished in diabetic hepatocytes, whereas the flux through the dehydrogenase was inversely correlated with the rate of endogenous ketogenesis. The same was observed in hepatocytes isolated from starved rats when branched-chain alpha-ketoacid oxidation was measured in the presence of added oleate. In both cases the diminished flux through the dehydrogenase, restored by a short preincubation of hepatocytes with insulin, was paralleled by a decrease of fatty acid-derived ketogenesis. The significance of these findings is discussed in relation to the role of insulin in branched-chain alpha-ketoacid oxidation in liver of diabetic rats. 相似文献
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Joanna Nakonieczna Ewelina Michta Magda Rybicka Mariusz Grinholc Anna Gwizdek-Wiśniewska Krzysztof P Bielawski 《BMC microbiology》2010,10(1):323