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1.
《Journal of molecular biology》2021,433(19):167162
Many proteins that can assemble into higher order structures termed amyloids can also concentrate into cytoplasmic inclusions via liquid–liquid phase separation. Here, we study the assembly of human Golgi-Associated plant Pathogenesis Related protein 1 (GAPR-1), an amyloidogenic protein of the Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP) protein superfamily, into cytosolic inclusions in Saccharomyces cerevisiae. Overexpression of GAPR-1-GFP results in the formation GAPR-1 oligomers and fluorescent inclusions in yeast cytosol. These cytosolic inclusions are dynamic and reversible organelles that gradually increase during time of overexpression and decrease after promoter shut-off. Inclusion formation is, however, a regulated process that is influenced by factors other than protein expression levels. We identified N-myristoylation of GAPR-1 as an important determinant at early stages of inclusion formation. In addition, mutations in the conserved metal-binding site (His54 and His103) enhanced inclusion formation, suggesting that these residues prevent uncontrolled protein sequestration. In agreement with this, we find that addition of Zn2+ metal ions enhances inclusion formation. Furthermore, Zn2+ reduces GAPR-1 protein degradation, which indicates stabilization of GAPR-1 in inclusions. We propose that the properties underlying both the amyloidogenic properties and the reversible sequestration of GAPR-1 into inclusions play a role in the biological function of GAPR-1 and other CAP family members. 相似文献
2.
3.
Margarita Burguera-Pascu Alberto Rodríguez-Archilla Pilar Baca 《Journal of trace elements in medicine and biology》2007,21(2):92-101
The antimicrobial efficacy of zinc (Zn) salts (sulfate and acetate) against Streptococcus mutans (S. mutans) present in the oral cavity was tested in this study. The substantivity of Zn salts was assessed by determining the concentration of Zn in whole, unstimulated saliva and by measuring the magnitude of suppression of salivary S. mutans, 2h after rinsing. The concentration of Zn was measured by atomic absorption spectrometry (AAS) with electrothermal atomization (ET AAS) in saliva sampled before (basal) and 24h after mouth rinsing with different concentrations of Zn (0.1%, 0.5% and 1%) administrated as sulfate and acetate. The estimation of Zn levels in samples collected 30, 60, 90 and 120 min after rinsing was carried out by AAS with flame atomization (FAAS). Immediately after rinsing, the concentration of Zn in saliva sharply increased with respect to the baseline values (0.055+/-0.017 mg/L), followed by a sustained decrease, probably due to clearance of salivary flow or swallowing during sampling. A significant reduction (>87%) in the total mean S. mutans counts was found 2h after rinsing either with sulfate or acetate solutions, as evidence of the high substantivity and effectiveness of the Zn salts tested. A statistically significant inverse relationship (p<0.001 and the Pearson correlation coefficients between -34% and -50%) was found between Zn levels and the respective pH values measured in the samples collected 60 and 120 min after rinsing, sustaining the theory of bacterial glycolysis inhibition. 相似文献
4.
Silvia Pastorekova Daniela Vullo Angela Casini Andrea Scozzafava Jaromir Pastorek Isao Nishimori 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):211-217
The tumor-associated transmembrane carbonic anhydrase (CA, EC 4.2.1.1) isozymes IX (CA IX) and XII (CA XII) are involved in acidification of hypoxic tumors, a process correlated with poor prognosis and clinical outcome of patients harboring such tumors. This process may be reversed by inhibiting these enzymes with potent sulfonamide/sulfamate inhibitors. A series of such aromatic/heterocyclic sulfonamides incorporating 2,3,5,6-tetrafluorobenzoyl-, 2,3,5,6-tetrafluoro- phenylsulfonyl- and pentafluorophenylureido moieties has been investigated for its interaction with the catalytic domain of the human isozymes hCA IX and hCA XII. Some of these compounds showed excellent inhibitory properties against both isozymes IX and XII, with several subnanomolar inhibitors detected for the first time. These sulfonamides may constitute valuable candidates for the development of novel antitumor therapies based on the inhibition of such tumor-associated CA isozymes. 相似文献
5.
Janitha A. Liyanage David M. Taylor David R. Williams 《Chemical Speciation and Bioavailability》2013,25(2):73-75
ABSTRACTA method has been developed for impregnating alginate-based wound dressings with trace elements required for wound healing and for quantifying the transfer from these dressing to wound fluid (for which a substitute—blood serum—was used in these experiments). Under ideal conditions, up to 85% can be carried across from the tow to the wound fluid. 相似文献
6.
A particle-induced X-ray emission (PIXE) analysis method is presented, which allows measurement of eight elements (i.e., K,
Ca, Mn, Fe, Cu, Zn, Se, and Rb) in human brain samples of only a few mg dry weight. The precision and accuracy of the method
were investigated by analyzing animal brain matter with both PIXE and instrumental neutron activation analysis (INAA). The
method was applied to measure the 8 elements in 46 different regions of 3 human brains. The sections analyzed originated from
either the left or the right cerebral hemisphere, brain stem, and cerebellum. For one of the brains, sections were also analyzed
from 26 corresponding regions of both hemispheres. For all elements, similar concentrations were found in the corresponding
areas of the left and right sides of the brain. The concentrations (in μg/g dry weight) of the elements K, Fe, Cu, Zn, Se,
and Rb were consistently higher in cortical structures than in white matter. Deep nuclei and brain stem, which have a mixed
composition, showed intermediate values for K, Zn, Se, and Rb. A hierarchical cluster analysis indicated that the various
brain regions clustered into two large groups, one comprising gray and mixed matter regions and the other, white and mixed
matter brain areas. 相似文献
7.
Kazimierz S. Kasprzak Michael P. Waalkes Lionel A. Poirier 《Biological trace element research》1987,13(1):253-273
Interactions between the physiologically essential metals calcium, magnesium, and zinc and the carcinogenic metals nickel
and cadmium were investigated to help elucidate the mechanisms of action of the carcinogenic metals. Bioassay studies revealed
several significant findings, including: (1) the ability of magnesium and calcium to inhibit nickel-induced elevation of pulmonary
adenoma incidence in strain A mice; (2) the ability of magnesium, but not of calcium, to prevent cadmium-induced subcutaneous
sarcoma formation; and (3) the ability of magnesium, but not of calcium, to inhibit nickel-induced muscle tumor formation.
Biochemical studies indicated a direct relationship between the antitumorigenic potential of magnesium and the capacity of
this metal to: (1) inhibit nickel and cadmium uptake by the target tissues in vivo; (2) inhibit nickel-induced disturbances
in DNA synthesis in vivo; (3) inhibit nuclear and cytosolic uptake of nickel by the target tissue cells in vivo; and (4) inhibit
nickel and cadmium binding to DNA in vitro. Calcium, which in most cases did not prevent carcinogenesis, had no consistent
influence on the uptake of carcinogenic metals or their biochemical effects in the target tissues. Magnesium and zinc, but
not calcium, were also found to attenuate the acute toxic effects of nickel, indicating a possible correlation between prevention
of acute effects and reduction in tumorigenicity. Zinc, which antagonizes cadmium tumorigenicity in the rat testis, was found
to reduce markedly cadmium uptake into isolated testicular interstitial cells. Also, zinc was found to inhibit strongly cadmium
binding to DNA in vitro. 相似文献
8.
Distribution of different forms of Zn in 16 acid alluvial rice growing soils of West Bengal (India) and their transformation
on submergence were studied. The results showed that more than 84% of total Zn occurred in the relatively inactive clay lattice-bound
form while a smaller fractionviz. 1.1, 1.6, 11.1 and 2.0 per cent of the total occurred as water-soluble plus exchangeable, organic complexed, amorphous sesquioxide-bound
and crystalline sesquioxide bound forms, respectively. All these four Zn forms showed significant negative correlations with
soil pH (r=−0.48**, −0.39*, −0.61** and −0.67**, respectively), while the latter two Zn forms showed significant positive correlations with Fe2O3 (0.68** and 0.88***) and Al2O3 (0.89*** and 0.75***) content of the soils. The different Zn forms were found to have positive and significant correlations amongst each other,
suggesting the existence of a dynamic equilibrium of these forms in soil.
Submergence caused an increase in the amorphous sesquioxide-bound form of Zn and a decrease in each of the other three forms.
The magnitude of such decreases in water-soluble plus exchangeable and crystalline sesquioxide-bound forms was found to be
correlated negatively with initial pH values of the soils and positively with the increase in the amorphous sesquioxide-bound
form, indicating their adsorption on the surface of the freshly formed hydrated oxides of Fe, which view was supported by
the existence of significant positive correlation between the increase in the amorphous sesquioxide-bound form of Zn and that
in AlCl3-extractable iron. The existence of a positive correlation between the decrease in crystalline sesquioxide-bound Zn and that
in Fe2O3 content in soil suggested that on waterlogging the soil Zn occluded in the cry talline sesquioxide was released as a result
of reduction of Fe2O3. 相似文献
9.
Rice (IR 42) was grown on two soils differing in zinc status for 30 days with and without Zn under submerged conditions in
pots. The fate of soil zinc was characterized by extraction of the soil successively with copper acetate and sodium hypochlorite
and by EUF extraction. Most of the applied zinc was extracted by copper acetate and represented as complexed fraction. There
exists a close and significnat relation between Cu(OAc)2-extractable zinc and Zn extracted by EUF for 5 minutes at 50 volts (r=0.98). The EUF-extractable zinc and Cu(OAc)2-extractable zinc were significantly correlated with the zinc content in the plant (r=0.82). The data from this investigation
suggest the possibility of Zn fractionation with the EUF technique and the fractions obtained agree closely to those determined
by chemical methods. The results obtained indicate that Zn in soil is held by weak organic bonding and that the extractions
by Cu(OAc)2 and/or EUF-5 minutes serve as a useful basis for extimating zinc availability in rice soils. 相似文献
10.
Theodor Günther Jürgen Vormann Jamaledin Ghaida 《Biological trace element research》1989,20(3):243-249
Application of salicylate increased the concentration of metallothionein (MT) in liver of pregnant rats as well as of adult male rats, whereas in fetal liver, MT was reduced by salicylate. Induction of MT synthesis by salicylate is an indirect effect because in cultured hepatocytes salicylate did not induce MT synthesis. Salicylate increased MT also in adrenalectomized rats. Indomethacin induced the same concentration of MT in maternal liver as salicylate. However, indomethacin had no effect on MT in fetal liver. Induction of MT in adult liver by salicylate and indomethacin was independent of zinc. 相似文献