Involvement of hepatic metallothioneins in hypozincemia associated with bacterial infection.

1978 ◽  
Vol 234 (4) ◽  
pp. E399 ◽  
Author(s):  
P Z Sobocinski ◽  
W J Canterbury ◽  
C A Mapes ◽  
R E Dinterman
Keyword(s):  
Amino Acid ◽  
Heat Stability ◽  
Acute Stage ◽  
Zinc Homeostasis ◽  
Zinc Binding ◽  
Live Vaccine Strain ◽  
Infectious Illness ◽  
Hepatic Synthesis ◽  
Major Amino Acid

Hypozincemia was induced in rats by Salmonella typhimurium and live vaccine strain Francisella tularensis (LVS) infections. Hepatic synthesis of zinc-binding proteins (ZBP) was studied in order to elucidate the mechanisms involved in the redistribution of zinc from plasma to liver occurring during infectious illness. ZBP, labeled in vivo with 65Zn, were isolated and identified as metallothioneins based, in part, on their heat stability, dimorphism, and amino acid composition. Cysteine was the major amino acid found in both forms of metallothionein and constituted 28-31% of total residues. The apparent half-life of these proteins as measured by disappearance of 65Zn was determined to be 19 h in a relatively mild infection (LVS) and 38 h in a more severe S. typhimurium infection. Results provide evidence that metallothioneins not only have the previously postulated regulatory role in normal zinc homeostasis but are intimately involved in the zinc redistribution occurring during the acute stage of infectious illness.

scholarly journals The First Histidine Triad Motif of PhtD Is Critical for Zinc Homeostasis inStreptococcus pneumoniae

2015 ◽  
Vol 84 (2) ◽  
pp. 407-415 ◽  
Author(s):  
Bart A. Eijkelkamp ◽  
Victoria G. Pederick ◽  
Charles D. Plumptre ◽  
Richard M. Harvey ◽  
Catherine E. Hughes ◽  
...  
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Zinc Homeostasis ◽  
Zinc Binding ◽  
Content Type ◽  
Metal Ion Homeostasis ◽  
Expression Studies ◽  
The Individual

Streptococcus pneumoniaeis the world's foremost human pathogen. Acquisition of the first row transition metal ion zinc is essential for pneumococcal colonization and disease. Zinc is acquired via the ATP-binding cassette transporter AdcCB and two zinc-binding proteins, AdcA and AdcAII. We have previously shown that AdcAII is reliant upon the polyhistidine triad (Pht) proteins to aid in zinc recruitment. Pht proteins generally contain five histidine (His) triad motifs that are believed to facilitate zinc binding and therefore play a significant role in pneumococcal metal ion homeostasis. However, the importance and potential redundancy of these motifs have not been addressed. We examined the effects of mutating each of the five His triad motifs of PhtD. The combination ofin vitrogrowth assays, active zinc uptake, and PhtD expression studies show that the His triad closest to the protein's amino terminus is the most important for zinc acquisition. Intriguingly,in vivocompetitive infection studies investigating the amino- and carboxyl-terminal His triad mutants indicate that the motifs have similar importance in colonization. Collectively, our new insights into the contributions of the individual His triad motifs of PhtD, and by extension the other Pht proteins, highlight the crucial role of the first His triad site in zinc acquisition. This study also suggests that the Pht proteins likely play a role beyond zinc acquisition in pneumococcal virulence.

Site Specific Incorporation of Amino Acid Analogues into Proteins In Vivo

2000 ◽  
Author(s):  
Anne K. Kowal ◽  
Caroline Kohrer ◽  
Uttam L. RajBhandary
Keyword(s):  
Amino Acid ◽  
Site Specific ◽  
Amino Acid Analogues

Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
The Other ◽  
Amino Acid Residues ◽  
Phase Synthesis ◽  
Other Hand ◽  
Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

Synthesis of Fragments of the Vasoactive Intestinal Peptide (VIP) and Analysis of Their Residual Biological Activities

1995 ◽  
Vol 60 (7) ◽  
pp. 1229-1235 ◽  
Author(s):  
Ivana Zoulíková ◽  
Ivan Svoboda ◽  
Jiří Velek ◽  
Václav Kašička ◽  
Jiřina Slaninová ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biological Activities ◽  
Residual Activity ◽  
Detailed Examination ◽  
Amino Acid Residues ◽  
Linear Peptide ◽  
Zone Electrophoresis ◽  
Capillary Zone

The vasoactive intestinal (poly)peptide (VIP) is a linear peptide containing 28 amino acid residues, whose primary structure indicates a low metabolic stability. The following VIP fragments, as potential metabolites, and their analogues were prepared by synthesis on a solid: [His(Dnp)1]VIP(1-10), VIP(11-14), [D-Arg12]VIP(11-14), [Lys(Pac)15,21,Arg20]VIP(15-22), and VIP(23-28). After purification, the peptides were characterized by amino acid analysis, mass spectrometry, RP HPLC, and capillary zone electrophoresis. In some tests, detailed examination of the biological activity of the substances in vivo and in vitro gave evidence of a low, residual activity of some fragments, viz. a depressoric activity in vivo for [His(Dnp)1]VIP(1-10) and a stimulating activity for the release of α-amylase in vitro and in vivo for [Lys(Pac)15,21,Arg20]VIP(15-22) and VIP(23-28).

ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes

2002 ◽  
Vol 283 (2) ◽  
pp. C569-C578 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Atp Release ◽  
Anion Channel ◽  
P2y Receptors ◽  
Cell Swelling ◽  
Channel Blockers ◽  
Medium Osmolarity ◽  
Subsequent Activation

Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the brain ATP is released by both neurons and astrocytes and participates in intercellular communication. We explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 μM) activated a small EAA release in 70–80% of the cultures tested. In both moderately (5% reduction of medium osmolarity) and substantially (35% reduction of medium osmolarity) swollen astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in nonswollen and moderately swollen cells was eliminated by a 5–10% increase in medium osmolarity or by anion channel blockers but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bidirectional neuron-astrocyte communication in vivo.

scholarly journals Sequence Comparison of Vaginolysin from Different Gardnerella Species

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 86
Author(s):  
Erin M. Garcia ◽  
Myrna G. Serrano ◽  
Laahirie Edupuganti ◽  
David J. Edwards ◽  
Gregory A. Buck ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Distinct Species ◽  
Vaginal Swab ◽  
Metagenomic Data ◽  
Gardnerella Vaginalis ◽  
Vaginal Epithelial Cells ◽  
Species Specific

Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo.

scholarly journals Studies on Aromatic Amino Acid Uptake by Rat Brain in Vivo

1962 ◽  
Vol 237 (3) ◽  
pp. 803-806
Author(s):  
Gordon Guroff ◽  
Sidney Udenfriend
Keyword(s):  
Amino Acid ◽  
Rat Brain ◽  
Aromatic Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake

scholarly journals Methionine and Arginine Supply Alters Abundance of Amino Acid, Insulin Signaling, and Glutathione Metabolism-Related Proteins in Bovine Subcutaneous Adipose Explants Challenged with N-Acetyl-d-sphingosine

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2114
Author(s):  
Yusheng Liang ◽  
Nana Ma ◽  
Danielle N. Coleman ◽  
Fang Liu ◽  
Yu Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Amino Acid ◽  
Insulin Signaling ◽  
Elongation Factor ◽  
In Vivo Studies ◽  
Glutathione Metabolism ◽  
Protein Abundance ◽  
Related Proteins ◽  
Subcutaneous Adipose

The objective was to perform a proof-of-principle study to evaluate the effects of methionine (Met) and arginine (Arg) supply on protein abundance of amino acid, insulin signaling, and glutathione metabolism-related proteins in subcutaneous adipose tissue (SAT) explants under ceramide (Ce) challenge. SAT from four lactating Holstein cows was incubated with one of the following media: ideal profile of amino acid as the control (IPAA; Lys:Met 2.9:1, Lys:Arg 2:1), increased Met (incMet; Lys:Met 2.5:1), increased Arg (incArg; Lys:Arg 1:1), or incMet plus incArg (Lys:Met 2.5:1 Lys:Arg 1:1) with or without 100 μM exogenous cell-permeable Ce (N-Acetyl-d-sphingosine). Ceramide stimulation downregulated the overall abundance of phosphorylated (p) protein kinase B (AKT), p-mechanistic target of rapamycin (mTOR), and p-eukaryotic elongation factor 2 (eEF2). Without Ce stimulation, increased Met, Arg, or Met + Arg resulted in lower p-mTOR. Compared with control SAT stimulated with Ce, increased Met, Arg, or Met + Arg resulted in greater activation of mTOR (p-mTOR/total mTOR) and AKT (p-AKT/total AKT), with a more pronounced response due to Arg. The greatest protein abundance of glutathione S-transferase Mu 1 (GSTM1) was detected in response to increased Met supply during Ce stimulation. Ceramide stimulation decreased the overall protein abundance of the Na-coupled neutral amino acid transporter SLC38A1 and branched-chain alpha-ketoacid dehydrogenase kinase (BCKDK). However, compared with controls, increased Met or Arg supply attenuated the downregulation of BCKDK induced by Ce. Circulating ceramides might affect amino acid, insulin signaling, and glutathione metabolism in dairy cow adipose tissue. Further in vivo studies are needed to confirm the role of rumen-protected amino acids in regulating bovine adipose function.

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