Abstract 422: Cardiovascular Regulation in Mice with Overexpression of the Gene of Vesicular Acetylcholine Transporter (VAChT)

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Geisa C Tezini ◽  
Silvia Guatimosim ◽  
Diogo A Guimarães ◽  
Mauro Oliveira ◽  
Rubens Fazan ◽  
...  
Keyword(s):  
Baroreflex Sensitivity ◽  
Fold Increase ◽  
Cardiovascular Regulation ◽  
Transgenic Animal ◽  
Vesicular Acetylcholine Transporter ◽  
Wild Type ◽  
Autonomic Blockade ◽  
Release Of Acetylcholine ◽  
Cardiovascular Autonomic Regulation ◽  
Spontaneous Baroreflex

It was recently developed a transgenic animal model with overexpression of cholinergic neurotransmission. This mouse, named ChAT-ChR2-EYFP, has several extra copies of the vesicular acetylcholine transporter (VAChT) gene and exhibits three-fold increase in the release of acetylcholine. However, the consequences of overexpression of VAChT protein to the cardiovascular system have not yet been characterized. Therefore, we have investigated the effects of the overexpression of the gene of VAChT on arterial pressure (AP) and heart rate (HR) as well as the autonomic cardiovascular regulation. Mice were assigned into two groups: Wild-type (WT, n=7) and ChAT-ChR2-EYFP (n=7). These animals were anesthetized (isoflurane) and implanted with probes to record AP by telemetry. After 10 days, the mice had basal AP and HR recorded continuously. Assessment of the autonomic function was conducted throughout the following approaches: 1) cardiac sympathovagal balance evaluated by HR responses to methylatropine and propranolol; 2) overall HR variability; 3) spontaneous baroreflex sensitivity by the sequence analysis. ChAT-ChR2-EYFP mice showed lower basal HR (461±8 vs. 502±14 bpm, p<0.01) but similar AP as compared to WT mice. ChAT-ChR2-EYFP mice exhibited higher vagal tone (Δbpm, 169±14 vs. 117±6, p=0.03) and lower HR after double autonomic blockade (IHR, 456±8 vs. 509±11 bpm, p<0.001). HR variability was similar between groups (SDNN: 88±16 vs. 65±7 ms; RMSSD: 11.4±1 vs. 9.7±0.5 ms). However, the baroreflex sensitivity (7.5±1.5 vs. 4.1±0.5 ms/mmHg, p=0.05) was higher in ChAT-ChR2-EYFP mice. Altogether, the results show that the cardiovascular autonomic regulation of ChAT-ChR2-EYFP mice is characterized by higher parasympathetic tone, combined with a lower basal HR and IHR. Moreover, these mice present greater baroreflex sensitivity.

Blood pressure of endothelin-3 null (-/-) knockout mice and endothelin A receptor null (-/-) knockout mice under anaesthesia

2002 ◽  
Vol 103 (s2002) ◽  
pp. 48S-52S ◽  
Author(s):  
Tomoyuki KUWAKI ◽  
Toru ISHII ◽  
Kihwan JU ◽  
Masashi YANAGISAWA ◽  
Yasuichiro FUKUDA
Keyword(s):  
Blood Pressure ◽  
Knockout Mice ◽  
Baroreflex Sensitivity ◽  
Cardiovascular Regulation ◽  
Wild Type ◽  
Rr Interval ◽  
Endothelin A Receptor ◽  
Eta Receptor ◽  
Endothelin 3 ◽  
The Relationship

Blood pressure (BP) and heart rate (HR) in endothelin-3 (ET-3) null (-/-) knockout mice and ETA receptor (-/-) mice were measured using the servo null pressure measuring technique under halothane anaesthesia. In infant ET-3 (-/-) mice (2–3 weeks old), mean BP and HR were 55±2mmHg and 436±30beats/min respectively. These values were not different from those in age-matched wild-type mice (53±3mmHg and 430±18beats/min respectively). Baroreflex sensitivity, which was calculated as the slope of the relationship between systolic BP and RR interval on an ECG, was also similar in ET-3 (-/-) mice (0.84±0.20ms/mmHg) and wild-type mice (1.07±0.38ms/mmHg). ETA receptor (-/-) mice were obtained by caesarean section on the expected day of delivery and tracheotomized, so that they would live for more than 24h. Mean BP and HR in ETA receptor (-/-) mice were 15±1mmHg and 333±6beats/min respectively. These values were not different from those in age-matched, similarly treated wild-type mice (16±3mmHg and 308±10beats/min respectively). Baroreflex sensitivity in the newborn ETA receptor (-/-) mice (0.45±0.15ms/mmHg) and wild-type mice (0.31±0.06ms/mmHg) were very low compared with the values in infant wild-type mice, but not different between the mutant mice and their littermates. Moreover, HR in awake ETA receptor (-/-) mice (396±13beats/min) was not different from that in wild-type mice (409±13beats/min). These results show that the ETA receptor and ET-3 are not involved in cardiovascular regulation, at least during the very early life of the mice. A possible involvement of the ETA receptor in BP regulation, if any, seems to occur at later times and/or in some pathological settings.

Autonomic Cardiovascular Regulation in the Newborn

2012 ◽  
pp. 201-221
Author(s):  
Peter Andriessen
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Heart Rate Response ◽  
Function Analysis ◽  
Feedback System ◽  
Cardiovascular Regulation ◽  
Interval Change ◽  
Method Transfer ◽  
Spontaneous Baroreflex

This paper reviews the baroreflex mediated heart rate response in human infants with a focus on data acquisition, signal processing and autonomic cardiovascular modeling. Baroreflex mediated heart rate response is frequently used as an estimate of autonomic cardiovascular regulation. Baroreflex mediated heart rate response may be viewed in terms of a negative-feedback system. To study fluctuations in this feedback system, continuous registration of ECG and blood pressure waveforms are required. From these waveforms, time series of R-R interval and blood pressure values are derived. This paper focus on spontaneous baroreflex sensitivity (e.g., R-R interval change per unit of arterial blood pressure change, ms/mmHg) calculated from cross-spectral analysis of spontaneous occurring changes in R-R interval and blood pressure. Despite different methodology (sequence method; transfer function analysis; head-up tilt) there is fairly good agreement of spontaneous baroreflex sensitivity values during homeostasis. Preterm infants and term newborns have values of 2-4 and 10-15 ms/mmHg, respectively. These values are much lower than found in adults, approximately 25 ms/mmHg. The clinical relevance of a limited baroreflex function may be that acute perturbations of the cardiovascular system are poorly counteracted and may result in poor cerebral perfusion.

scholarly journals Functional expression of a yeast mitochondrial intron-encoded protein requires RNA processing at a conserved dodecamer sequence at the 3' end of the gene.

1989 ◽  
Vol 9 (4) ◽  
pp. 1507-1512 ◽  
Author(s):  
H Zhu ◽  
H Conrad-Webb ◽  
X S Liao ◽  
P S Perlman ◽  
R A Butow
Keyword(s):  
Genetic Analysis ◽  
Rna Processing ◽  
Fold Increase ◽  
Functional Expression ◽  
Rrna Gene ◽  
Yeast Mitochondria ◽  
Wild Type ◽  
Site Specific ◽  
Var1 Gene ◽  
A Site

All mRNAs of yeast mitochondria are processed at their 3' ends within a conserved dodecamer sequence, 5'-AAUAAUAUUCUU-3'. A dominant nuclear suppressor, SUV3-I, was previously isolated because it suppresses a dodecamer deletion at the 3' end of the var1 gene. We have tested the effects of SUV3-1 on a mutant containing two adjacent transversions within a dodecamer at the 3' end of fit1, a gene located within the 1,143-base-pair intron of the 21S rRNA gene, whose product is a site-specific endonuclease required in crosses for the quantitative transmission of that intron to 21S alleles that lack it. The fit1 dodecamer mutations blocked both intron transmission and dodecamer cleavage, neither of which was suppressed by SUV3-1 when present in heterozygous or homozygous configurations. Unexpectedly, we found that SUV3-1 completely blocked cleavage of the wild-type fit1 dodecamer and, in SUV3-1 homozygous crosses, intron conversion. In addition, SUV3-1 resulted in at least a 40-fold increase in the amount of excised intron accumulated. Genetic analysis showed that these phenotypes resulted from the same mutation. We conclude that cleavage of a wild-type dodecamer sequence at the 3' end of the fit1 gene is essential for fit1 expression.

scholarly journals The TonB system in Aeromonas hydrophila NJ-35 is essential for MacA2B2 efflux pump-mediated macrolide resistance

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Yuhao Dong ◽  
Qing Li ◽  
Jinzhu Geng ◽  
Qing Cao ◽  
Dan Zhao ◽  
...  
Keyword(s):  
Aeromonas Hydrophila ◽  
Efflux Pump ◽  
Fold Increase ◽  
Activity Level ◽  
Macrolide Resistance ◽  
Wild Type ◽  
Iron Deprivation ◽  
Pump Activity ◽  
Tonb System ◽  
Increased Sensitivity

AbstractThe TonB system is generally considered as an energy transporting device for the absorption of nutrients. Our recent study showed that deletion of this system caused a significantly increased sensitivity of Aeromonas hydrophila to the macrolides erythromycin and roxithromycin, but had no effect on other classes of antibiotics. In this study, we found the sensitivity of ΔtonB123 to all macrolides tested revealed a 8- to 16-fold increase compared with the wild-type (WT) strain, but this increase was not related with iron deprivation caused by tonB123 deletion. Further study demonstrated that the deletion of tonB123 did not damage the integrity of the bacterial membrane but did hinder the function of macrolide efflux. Compared with the WT strain, deletion of macA2B2, one of two ATP-binding cassette (ABC) types of the macrolide efflux pump, enhanced the sensitivity to the same levels as those of ΔtonB123. Interestingly, the deletion of macA2B2 in the ΔtonB123 mutant did not cause further increase in sensitivity to macrolide resistance, indicating that the macrolide resistance afforded by the MacA2B2 pump was completely abrogated by tonB123 deletion. In addition, macA2B2 expression was not altered in the ΔtonB123 mutant, indicating that any influence of TonB on MacA2B2-mediated macrolide resistance was at the pump activity level. In conclusion, inactivation of the TonB system significantly compromises the resistance of A. hydrophila to macrolides, and the mechanism of action is related to the function of MacA2B2-mediated macrolide efflux.

scholarly journals Nonrecombinant meiosis I nondisjunction in Saccharomyces cerevisiae induced by tRNA ochre suppressors.

Genetics ◽  
1989 ◽  
Vol 123 (1) ◽  
pp. 81-95 ◽  
Author(s):  
E J Louis ◽  
J E Haber
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mitotic Chromosome ◽  
Stop Codon ◽  
Fold Increase ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Nonsense Mutations ◽  
Chromosome Iii ◽  
Meiosis I ◽  
Chromosome Nondisjunction

Abstract The presence of the tRNA ochre suppressors SUP11 and SUP5 is found to induce meiosis I nondisjunction in the yeast Saccharomyces cerevisiae. The induction increases with increasing dosage of the suppressor and decreases in the presence of an antisuppressor. The effect is independent of the chromosomal location of SUP11. Each of five different chromosomes monitored exhibited nondisjunction at frequencies of 0.1%-1.1% of random spores, which is a 16-160-fold increase over wild-type levels. Increased nondisjunction is reflected by a marked increase in tetrads with two and zero viable spores. In the case of chromosome III, for which a 50-cM map interval was monitored, the resulting disomes are all in the parental nonrecombinant configuration. Recombination along chromosome III appears normal both in meioses that have no nondisjunction and in meioses for which there was nondisjunction of another chromosome. We propose that a proportion of one or more proteins involved in chromosome pairing, recombination or segregation are aberrant due to translational read-through of the normal ochre stop codon. Hygromycin B, an antibiotic that can suppress nonsense mutations via translational read-through, also induces nonrecombinant meiosis I nondisjunction. Increases in mistranslation, therefore, increase the production of aneuploids during meiosis. There was no observable effect of SUP11 on mitotic chromosome nondisjunction; however some disomes caused SUP11 ade2-ochre strains to appear white or red, instead of pink.

scholarly journals Phosphoglycolate has profound metabolic effects but most likely no role in a metabolic DNA response in cancer cell lines

2019 ◽  
Vol 476 (4) ◽  
pp. 629-643 ◽  
Author(s):  
Isabelle Gerin ◽  
Marina Bury ◽  
Francesca Baldin ◽  
Julie Graff ◽  
Emile Van Schaftingen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Oxidative Dna Damage ◽  
Fold Increase ◽  
Metabolic Effects ◽  
Phosphoglycerate Mutase ◽  
Wild Type ◽  
Metabolic Disturbances ◽  
Phosphoglycolate Phosphatase ◽  
Damage Repair

Abstract Repair of a certain type of oxidative DNA damage leads to the release of phosphoglycolate, which is an inhibitor of triose phosphate isomerase and is predicted to indirectly inhibit phosphoglycerate mutase activity. Thus, we hypothesized that phosphoglycolate might play a role in a metabolic DNA damage response. Here, we determined how phosphoglycolate is formed in cells, elucidated its effects on cellular metabolism and tested whether DNA damage repair might release sufficient phosphoglycolate to provoke metabolic effects. Phosphoglycolate concentrations were below 5 µM in wild-type U2OS and HCT116 cells and remained unchanged when we inactivated phosphoglycolate phosphatase (PGP), the enzyme that is believed to dephosphorylate phosphoglycolate. Treatment of PGP knockout cell lines with glycolate caused an up to 500-fold increase in phosphoglycolate concentrations, which resulted largely from a side activity of pyruvate kinase. This increase was much higher than in glycolate-treated wild-type cells and was accompanied by metabolite changes consistent with an inhibition of phosphoglycerate mutase, most likely due to the removal of the priming phosphorylation of this enzyme. Surprisingly, we found that phosphoglycolate also inhibits succinate dehydrogenase with a Ki value of <10 µM. Thus, phosphoglycolate can lead to profound metabolic disturbances. In contrast, phosphoglycolate concentrations were not significantly changed when we treated PGP knockout cells with Bleomycin or ionizing radiation, which are known to lead to the release of phosphoglycolate by causing DNA damage. Thus, phosphoglycolate concentrations due to DNA damage are too low to cause major metabolic changes in HCT116 and U2OS cells.

scholarly journals Engineering Desiccation Tolerance inEscherichia coli

2000 ◽  
Vol 66 (4) ◽  
pp. 1680-1684 ◽  
Author(s):  
Daniela Billi ◽  
Deborah J. Wright ◽  
Richard F. Helm ◽  
Todd Prickett ◽  
Malcolm Potts ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Phase Transition ◽  
Freeze Drying ◽  
Fold Increase ◽  
Inescherichia Coli ◽  
Vibration Frequencies ◽  
Wild Type ◽  
Air Drying ◽  
Phase Transition Temperatures ◽  
Cell Dehydration

ABSTRACT Recombinant sucrose-6-phosphate synthase (SpsA) was synthesized inEscherichia coli BL21DE3 by using the spsA gene of the cyanobacterium Synechocystis sp. strain PCC 6803. Transformants exhibited a 10,000-fold increase in survival compared to wild-type cells following either freeze-drying, air drying, or desiccation over phosphorus pentoxide. The phase transition temperatures and vibration frequencies (PO stretch) in phospholipids suggested that sucrose maintained membrane fluidity during cell dehydration.

scholarly journals OmpR and LeuO Positively Regulate the Salmonella enterica Serovar Typhi ompS2 Porin Gene

2004 ◽  
Vol 186 (10) ◽  
pp. 2909-2920 ◽  
Author(s):  
Marcos Fernández-Mora ◽  
José Luis Puente ◽  
Edmundo Calva
Keyword(s):  
Salmonella Enterica ◽  
Type Strain ◽  
Wild Type Strain ◽  
Phosphorylation Site ◽  
Regulatory Region ◽  
Random Mutagenesis ◽  
Fold Increase ◽  
Upstream Regulatory Region ◽  
Wild Type ◽  
Transposon Insertion

ABSTRACT The Salmonella enterica serovar Typhi ompS2 gene codes for a 362-amino-acid outer membrane protein that contains motifs common to the porin superfamily. It is expressed at very low levels compared to the major OmpC and OmpF porins, as observed for S. enterica serovar Typhi OmpS1, Escherichia coli OmpN, and Klebsiella pneumoniae OmpK37 quiescent porins. A region of 316 bp, between nucleotides −413 and −97 upstream of the transcriptional start point, is involved in negative regulation, as its removal resulted in a 10-fold increase in ompS2 expression in an S. enterica serovar Typhi wild-type strain. This enhancement in expression was not observed in isogenic mutant strains, which had specific deletions of the regulatory ompB (ompR envZ) operon. Furthermore, ompS2 expression was substantially reduced in the presence of the OmpR D55A mutant, altered in the major phosphorylation site. Upon random mutagenesis, a mutant where the transposon had inserted into the upstream regulatory region of the gene coding for the LeuO regulator, showed an increased level of ompS2 expression. Augmented expression of ompS2 was also obtained upon addition of cloned leuO to the wild-type strain, but not in an ompR isogenic derivative, consistent with the notion that the transposon insertion had increased the cellular levels of LeuO and with the observed dependence on OmpR. Moreover, LeuO and OmpR bound in close proximity, but independently, to the 5′ upstream regulatory region. Thus, the OmpR and LeuO regulators positively regulate ompS2.

Modulation of carotid baroreflex responsiveness in man: effects of posture and propranolol

1976 ◽  
Vol 41 (3) ◽  
pp. 383-387 ◽  
Author(s):  
D. L. Eckberg ◽  
F. M. Abboud ◽  
A. L. Mark
Keyword(s):  
Angina Pectoris ◽  
Supine Position ◽  
Baroreflex Sensitivity ◽  
Pulse Interval ◽  
Upright Posture ◽  
Adrenergic Stimulation ◽  
Interval Prolongation ◽  
Carotid Baroreflex ◽  
Before And After ◽  
Autonomic Blockade

Carotid baroreceptors were stimulated with graded neck suction in supine and standing volunteers, before and after autonomic blockade, to determine the influence of posture on baroreflex responsiveness. Propranolol significantly augmented baroreflex pulse interval prolongation in the supine position. Upright posture did not modify baroreflex pulse interval responses prior to propranolol, but significantly augmented responses after propranolol. The results suggest that standing enhances baroreflex sensitivity, but that under normal circumstances, this effect is masked by beta-adrenergic stimulation. Augmentation of baroreflex pulse interval prolongation in the supine and standing positions by propranolol may contribute to the effectiveness of this drug in angina pectoris and labile hypertension.

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