1,721,017 research outputs found
α-L-Fucosidase activity in endometrial, cervical and ovarian cancer
No full textalpha-L-fucosidase activity assayed on endometrial, cervical and ovarian tissue in benign and malignant conditions has been found to be increased in cancer tissue. Knowing that alpha-L-fucose plays a fundamental role in the process of inhibition of macrophages migration, increased activity of fucosidase in tumors can be interpreted as a possible mechanism by which cancer cells directly subvert the process of macrophages activation thus facilitating xenoplastic growth
Adenylyl cyclases as innovative therapeutic goals.
No full textPharmacological modulation of intracellular cyclic AMP (cAMP) signalling could provide new therapeutic and experimental tools. Although drugs interfering with this pathway have traditionally targeted membrane receptors, the effector enzyme adenylyl cyclase (AC), which functions as a signalling catalyst, also presents an interesting target. Thus, development of isoform
selective stimulator and/or inhibitor compounds for AC could lead to organ-specific pharmacotherapeutics for treating heart failure, cancer, and neurodegenerative diseases. In this review, the potential of AC as the object of drug therapy is discussed
HSP70 Expression in Human Trophoblast Cells Exposed to Different 1.8 GHz Mobile Phone Signals
No full textThe heat-shock proteins (HSPs) are important cellular
stress markers and have been proposed as candidates to infer
biological effects of high-frequency electromagnetic fields
(EMFs). In the current study, HSP70 gene and protein expression
were evaluated in cells of the human trophoblast cell
line HTR-8/SVneo after prolonged exposure (4 to 24 h) to 1.8
GHz continuous-wave (CW) and different GSM signals
(GSM-217Hz and GSM-Talk) to assess the possible effects of
time and modulation schemes on cell responses. Inducible
HSP70 protein expression was not modified by high-frequency
EMFs under any condition tested. The inducible HSP70A,
HSP70B and the constitutive HSC70 transcripts did not
change in cells exposed to high-frequency EMFs with the different
modulation schemes. Instead, levels of the inducible
HSP70C transcript were significantly enhanced after 24 h exposure
to GSM-217Hz signals and reduced after 4 and 16 h
exposure to GSM-Talk signals. As in other cell systems, in
HTR-8/SVneo cells the response to high-frequency EMFs was
detected at the mRNA level after exposure to amplitude-modulated GSM signals. The present results suggest that the expression
analysis for multiple transcripts, though encoding the
same or similar protein products, can be highly informative
and may account for subtle changes not detected at the protein
level
alpha-adrenoceptor-mediated glucose release from perifused catfish hepatocytes
No full textIn fish liver catecholamines bind to β-adrenoceptors (AR) and increase glucose release via cAMP augmentation, α1 -AR have recently been shown to mediate IP3 and Ca2+ elevation in catfish and eel hepatocytes, although their coupling to a physiological response has remained doubtful. We have perifused isolated catfish hepatocytes in Bio-Gel P4 columns with epinephrine in the presence of prazosin and/or propranolol, α- and β-AR antagonists, respectively. Ten nM epinephrine stimulated glucose release approximately 3- fold, and this effect was completely antagonized by the simultaneous presence of both α- and β-AR blockers. The two AR antagonists separately inhibited about one-third and two-third of the total stimulation, respectively. Through α-AR occupancy, epinephrine provoked a significant increase of glucose release whereas no stimulation was detected in Ca2+-depleted hepatocytes. Glucose release was strongly elevated by both ionomycin and dibutyryl cAMP. These results represent the first direct evidence that α-AR transduction pathway is involved in epinephrine-induced glucose release from fish hepatocytes
The role and modulation of the oxidative balance in pregnancy
No full textOxidative processes exert a fundamental regulatory function during pregnancy. It depends on the influence of oxygen, nitric oxide, reactive oxygen species and reactive nitrogen species metabolic pathways upon the vascular changes in the maternal organism, as well as on the regulation of uterine and cervical tone throughout gestation and delivery. These functions are strictly linked with the mediators of the inflammatory pathway. At the beginning of pregnancy, when a certain grade of inflammatory change is necessary to the trophoblast invasion of maternal tissue, the activation of the process by nitric oxide and reactive nitrogen species is welcome. Indeed, these products modulate the metalloproteinases, which are responsible for the remodelling of uterine extracellular matrix. At this stage estrogens are involved as well in the regulation of the delicate balance of pro-oxidant and anti-oxidant effects. Furthermore, reactive oxygen and nitrogen species appear to play an important role both in normal and pathologic embryogenesis. During advanced pregnancy, a derangement of the oxidative balance can lead to the improper activation of inflammatory changes, thus triggering premature labour as well as other complications, such as foetal growth restriction and preeclampsia. Although a number of pro- and anti-oxidant agents are available to influence the above-mentioned processes, there is no way to adequately measure the oxidative needs in single cases, in order to modulate the oxidative balance in clinical practice. Pharmacological research should be addressed to the development of new drugs, as well as to selective methods of delivery to the gestational tissues
Adenylyl cyclase activity and glucose release from the liver of the European eel, Anguilla anguilla
No full textThe properties of adenylyl cyclase (AC) in liver membranes of the European eel (Anguilla anguilla) and the involvement of cAMP in glucose release from isolated hepatocytes in response to catecholamines were studied. Basal enzyme activity seemed essentially unaffected by GTP, while a biphasic response to increasing nucleotide concentrations was obtained in the presence of epinephrine. Eel liver AC was dose-dependently stimulated by guanosine 5'- O-(3-thiotriphosphate) and inhibited by guanosine 5'-O-(2-thiodiphosphate). AC activity, intracellular cAMP levels, and glucose release from isolated hepatocytes were significantly enhanced by NaF, forskolin, epinephrine, and phenylephrine. The rise in cAMP production stimulated by catecholamines was counteracted by propranolol, but not by phentolamine. Catecholamine-induced glucose output was instead partially antagonized by both phentolamine and propranolol. Complete inhibition was obtained only by the simultaneous presence of the two adrenergic antagonists. Glucose release from the cells was induced by dibutyryl cAMP and by the calcium ionophore ionomycin. In summary, these data provide the first characterization of eel liver AC system and suggest a direct role for cAMP in the catecholamine-dependent glucose output. Furthermore, the involvement of calcium ions in this cellular response is hypothesized
Evidence for a circadian clock in HRPE cells controlling adenylyl cyclase activity rhythms
No full textCircadian clocks regulate adenylyl cyclase activity rhythms in human RPE cells
No full textGenes and components of the circadian clock may represent relevant drug targets for diseases involving circadian dysfunctions. By exploiting an established cell line derived from human retinal pigment epithelium (HRPE), the cell constituting the blood-retinal barrier that is essential to maintain the visual functions of the sensorineural retina, we showed serum-shock induction of rhythmic changes in forskolin-evoked adenylyl cyclase (AC) activity. In the presence of Ca2+ and protein kinase A, the forskolin-induced AC activity is significantly, but not completely inhibited, suggesting the involvement of both Ca2+-sensitive and Ca2+-insensitive AC isoforms in the regulation of circadian rhythmicity in these cells. Semi-quantitative RT-PCR showed circadian profile in the expression of three AC isoforms, the Ca2+-inhibitable AC5 and AC6 and the Ca2+-insensitive AC7, and the clock genes hPer1 and hPer2. Our results demonstrate for the first time circadian rhythmicity in a human cell line, identifying the isoforms involved in the circadian profile of AC activity and showing a rhythmicity of the clock gene mRNA expression in these cells. Therefore, the results reported here provide evidence for an intertwine between AC/[Ca2+]i signalling pathways and Per genes in the HRPE circadian clockwork
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