scholarly journals Long-term effect of cyclic AMP on N-glycosylation is caused by an increase in the activity of the cis-prenyltransferase

1996 ◽  
Vol 316 (2) ◽  
pp. 575-581 ◽  
Author(s):  
Matthias KONRAD ◽  
Wolfgang E. MERZ

Previously we have shown that long-term pretreatment of JEG-3 choriocarcinoma cells with 8-bromo-cAMP increases the capacity for N-glycosylation that was caused by an 8–10-fold enlargement of the dolichol pyrophosphoryl oligosaccharide (Dol-PP-oligosaccharide) pool [Konrad and Merz (1994) J. Biol. Chem. 269, 8659–8666]. The factors involved in the effect of cAMP on synthesis of Dol-PP-oligosaccharide are investigated here. The GlcNAc transfer to dolichol phosphate (Dol-P) was found to be unaffected by pretreatment with 8-bromo-cAMP. By measuring the uptake of [3H]mevalonate, a 20-fold increase in the incorporation of the label into Dol-P was observed in the cells treated with 8-bromo-cAMP. Under the same conditions, the synthesis of dolichol was enhanced 60-fold. However, the incorporation of the radioactivity into cholesterol was not increased in the JEG-3 cells pretreated with 8-bromo-cAMP, which suggests a specific stimulation of the dolichol/Dol-P pathway by cAMP. The cis-prenyltransferase activity was found to be increased 10-fold in cells pretreated with 8-bromo-cAMP. Dolichol kinase activity was unaffected by stimulation with 8-bromo-cAMP. The present study suggests that the larger glycosylation capacity in JEG-3 cells treated with 8-bromo-cAMP is caused by an increase in the microsomal cis-prenyltransferase activity.

1978 ◽  
Vol 88 (2) ◽  
pp. 274-284 ◽  
Author(s):  
Alberto J. Carrillo ◽  
Charles H. Sawyer

ABSTRACT The internal variations (i. e. in timing, duration and amplitude) of the LH surge mechanism within individual rats were examined by monitoring from 3 to 7 successive pro-oestrous LH surges in each of 5 regular 4-day cycling rats fitted with chronic intravenous cannulas. On each successive pro-oestrus blood was collected (0.5–0.6 ml hourly from 14.00–21.00) for radioimmunoassay of LH. The surgery of cannulation had no long-term effect on the regularity of the oestrous cycle. Two rats did, however, show briefly irregular cycles, including one with a 9-day period of anoestrus (pseudopregnancy). In three of the five rats successive pro-oestrous plasma LH curves (4 in one and 3 each in the other two) were internally very consistent in timing, shape and amplitude, However, between each 2 of these 3 animals there were distinct differences in the LH secretory patterns, by as much as 2 h in timing of the onset of the surge and its peak amplitude. The first two surges of the other two rats were atypical of their subsequent surges, which were mostly consistent in timing and amplitude. The pro-oestrous LH surge following the 9-day period of anoestrus was advanced by 2 h and elevated to twice the mean peak amplitude of the cyclic LH surges in that rat. Subsequently, post-PSP surges were studied in rats made pseudopregnant by mechanical stimulation of the cervix. In all cases the immediate post-PSP surge occurred earlier in the afternoon and with a greater peak amplitude than the subsequent cyclic LH surge in the same rat.


2018 ◽  
Vol 89 (9) ◽  
pp. 989-994 ◽  
Author(s):  
Tao Xie ◽  
Lisa Bloom ◽  
Mahesh Padmanaban ◽  
Breanna Bertacchi ◽  
Wenjun Kang ◽  
...  

ObjectiveTo evaluate the long-term effect of 60 Hz stimulation of the subthalamic nucleus (STN) on dysphagia, freezing of gait (FOG) and other motor symptoms in patients with Parkinson’s disease (PD) who have FOG at the usual 130 Hz stimulation.MethodsThis is a prospective, sequence randomised, crossover, double-blind study. PD patients with medication refractory FOG at 130 Hz stimulation of the STN were randomised to the sequences of 130 Hz, 60 Hz or deep brain stimulation off to assess swallowing function (videofluoroscopic evaluation and swallowing questionnaire), FOG severity (stand–walk–sit test and FOG questionnaire) and motor function (Unified PD Rating Scale, Part III motor examination (UPDRS-III)) at initial visit (V1) and follow-up visit (V2, after being on 60 Hz stimulation for an average of 14.5 months), in their usual medications on state. The frequency of aspiration events, perceived swallowing difficulty and FOG severity at 60 Hz compared with 130 Hz stimulation at V2, and their corresponding changes at V2 compared with V1 at 60 Hz were set as primary outcomes, with similar comparisons in UPDRS-III and its subscores as secondary outcomes.ResultsAll 11 enrolled participants completed V1 and 10 completed V2. We found the benefits of 60 Hz stimulation compared with 130 Hz in reducing aspiration frequency, perceived swallowing difficulty, FOG severity, bradykinesia and overall axial and motor symptoms at V1 and persistent benefits on all of them except dysphagia at V2, with overall decreasing efficacy when comparing V2 to V1.ConclusionsThe 60 Hz stimulation, when compared with 130 Hz, has long-term benefits on reducing FOG, bradykinesia and overall axial and motor symptoms except dysphagia, although the overall benefits decrease with long-term use.Clinical trial registrationNCT02549859; Pre-results.


1986 ◽  
Vol 238 (3) ◽  
pp. 653-661 ◽  
Author(s):  
J G Altin ◽  
F L Bygrave

A perfused liver system incorporating a Ca2+-sensitive electrode was used to study the long-term effects of glucagon and cyclic AMP on the mobilization of Ca2+ induced by phenylephrine, vasopressin and angiotensin. At 1.3 mM extracellular Ca2+ the co-administration of glucagon (10 nM) or cyclic AMP (0.2 mM) and a Ca2+-mobilizing hormone led to a synergistic potentiation of Ca2+ uptake by the liver, to a degree which was dependent on the order of hormone administration. A maximum net amount of Ca2+ influx, corresponding to approx. 3800 nmol/g of liver (the maximum rate of influx was 400 nmol/min per g of liver), was induced when cyclic AMP or glucagon was administered about 4 min before vasopressin and angiotensin. These changes are over an order of magnitude greater than those induced by Ca2+-mobilizing hormones alone [Altin & Bygrave (1985) Biochem. J. 232, 911-917]. For a maximal response the influx of Ca2+ was transient and was essentially complete after about 20 min. Removal of the hormones was followed by a gradual efflux of Ca2+ from the liver over a period of 30-50 min; thereafter, a similar response could be obtained by a second administration of hormones. Dose-response measurements indicate that the potentiation of Ca2+ influx by glucagon occurs even at low (physiological) concentrations of the hormone. By comparison with phenylephrine, the stimulation of Ca2+ influx by vasopressin and angiotensin is more sensitive to low concentrations of glucagon and cyclic AMP, and can be correlated with a 20-50-fold increase in the calcium content of mitochondria. The reversible uptake of such large quantities of Ca2+ implicates the mitochondria in long-term cellular Ca2+ regulation.


2010 ◽  
Author(s):  
Andreas T. Breuer ◽  
Michael E. J. Masson ◽  
Glen E. Bodner
Keyword(s):  

Sign in / Sign up

Export Citation Format

Share Document