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1.
PrPC is associated with a variety of functions, and its ability to interact with a multitude of partners, including itself, may largely explain PrP multifunctionality and the lack of consensus on the genuine physiological function of the protein in vivo. In contrast, there is a consensus in the literature that alterations in PrPC trafficking and intracellular retention result in neuronal degeneration. In addition, a proteolytic modification in the late secretory pathway termed the α-cleavage induces the secretion of PrPN1, a PrPC-derived metabolite with fascinating neuroprotective activity against toxic oligomeric Aβ molecules implicated in Alzheimer disease. Thus, studies focusing on understanding the regulation of PrPC trafficking to the cell surface and the modulation of α-cleavage are essential. The objective of this commentary is to highlight recent evidences that PrPC homodimerization stimulates trafficking of the protein to the cell surface and results in high levels of PrPN1 secretion. We also discuss a hypothetical model for these results and comment on future challenges and opportunities. 相似文献
2.
P Favard N Favard Q L Zhu J Bourguet J P Lechaire 《Biology of the cell / under the auspices of the European Cell Biology Organization》1989,66(1-2):99-106
We have developed a technique for recovering apical membranous sheets from amphibian urinary bladders by gelatin stripping. The tissue is mounted on a lucite support and the apical surface is first stuck onto a gelatin-coated glass slide at 30 degrees C. This sandwich is then chilled on ice and the bladder is pulled away from the slide. Preliminary results indicate that this simple technique could be used to remove membranous apical sheets of various sizes, almost devoid of cytoplasmic contamination and without significant damage to the underlying cell structures. The method could also be adapted to prepare perforated cells and to study the cohesive forces between the different layers of the tissue. 相似文献
3.
G Calamita J Bourguet J S Hugon J Fischbarg 《Biology of the cell / under the auspices of the European Cell Biology Organization》1989,66(1-2):29-36
3,3'-diallyldiethylstilbestrol (DADES), a blocker of the facilitated diffusion of glucose, was found to interfere markedly with the hydrosmotic response to antidiuretic hormone and its related agonists. Frog urinary bladders were isolated and monitored for transmural net water flow. DADES was added either to the serosal or to the apical medium at concentrations ranging from 10(-4) M to 10(-6) M. Pretreatment for 30 min with apical 10(-4) M DADES drastically reduced the subsequent hydrosmotic response: (a) to oxytocin (4.4 x 10(-8) M) by 91.7 +/- 17.6% versus 6.2 +/- 7.8 in control; (b) to 8-bromo 3',5'-cyclic AMP by 93.5 +/- 19.4% versus 19.4 +/- 11.4%; (c) to serosal hyperosmolarity (mannitol 220 mOsm) by 99.3 +/- 0.5% versus 12.3 +/- 18.2%. This effect was dose-dependent. Inhibitory action of DADES was more effective on the apical side than on the serosal side (97.0 +/- 1.5 versus 45.8 +/- 10.8). Freeze-fracture studies revealed a modified distribution of the particles and unusual endocytotic pits and vesicles in the apical membrane of both granular and mitochondria-rich epithelial cells. These observations point to multiple and complex effects of the drug. Thus, it seems that DADES has numerous effects on urinary epithelium, which makes it a nonspecific inhibitor of water permeation. Conclusions on its use should therefore be drawn with suitable caution. 相似文献
4.
Role of vesicular transport in ADH-stimulated aggregate delivery 总被引:1,自引:0,他引:1
5.
Valérie Maxime Jean-Pierre Pennec Claude Peyraud 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1991,161(6):557-568
Summary The effects of increased ambient salinity (35 mg · ml-1) were studied at 1, 6, and 24 h after direct transfer of rainbow trout from freshwater to seawater. Two series of experiments were carried out successively. The first series was designed to simultaneously study all the respiratory (except Hb affinity for O2), circulatory, and acid-base variables in each fish. In this series, fish were fitted with catheters chronically inserted into the cardiac bulbus, the dorsal aorta, and the opercular and buccal cavities. In the second series, designed to study haemoglobin O2 affinity, fish were fitted with only a dorsal aorta catheter. The ventilatory flow (
) was markedly increased just after transfer (by 55% at 1 h), then more moderately (by 20% at 6 h and 32% at 24 h). The initial hyperventilation peak was associated with frequent couphing motions. These ventilatory changes resulted essentially from increase in ventilatory amplitude. Initially, standard oxygen consumption (MM}O2) decreased slightly, the moderately increased (by 12% at 24 h), so that the oxygen convection requirement (
) increased substantially. In spite of an increased ventilation, the partial pressure of oxygen in arterial blood (P
aO2) decreased slightly at 1 h, prior to returning to control levels, while partial pressure of carbon dioxide in arterial blood (P
aCO2) was not significantly decreased. Gill oxygen transfer factor decreased substantially at 1 h (by 35%) then more moderately (by 7% at 1 h and 12% at 24 h). These results suggest a decrease in gas diffusing capacity of the gills. As P
aCO2 remained approximatively unchanged, the gradual decrease in arterial pH (pHa) from 7.94 to 7.67 at 24 h must therefore be regarded as a metabolic acidosis. The strong ion difference decreased markedly because the concentration of plasma chloride increased more than that of sodium. Arterial O2 content (C
aO2) gradually decreased (by 38% at 24 h) simultaneously with the decrease in pHa, while the ratio P
aO2/C
aO2 increased. In parallel, seawater exposure induced a marked decrease in affinity of haemoglobin for O2, so that at 24 h, P50 was increased by 26% above the value obtained in freshwater-adapted trout. The increase in
could be ascribed initially (at 1 h) to the decrease of P
aO2 and later to a stimulation of respiratory neurons resulting from the lowered medullary interstitial pH. The decrease in C
aO2 could be interpreted mainly as a consequence of a decreased affinity of haemoglobin for O2, likely to be due to the blood acidosis and a predictable increase in chloride concentration within erythrocytes. Cardiac output (
) slightly decreased at 1 h, then progressively increased by 30% at 24 h. Branchial vascular resistance increased at 1 h by 28%, then decreased by 18% of the control value at 24 h. Systemic vascular resistance decreased markedly by 40% at 24 h. As heart rate (HR) remained significantly unchanged, the cardiac stroke volume initially decreased then increased in relation to the changes in
. The increase of
, allowing compensation for the effect of decreased C
aO2 in tissue O2 supply, was interpreted as a passive consequence of the decrease in total vascular resistance occurring during seawater exposure.Abbreviations a.u.
arbitrary units
-
C
aO2
arterial oxygen content
- pH50
arterial pH at P50
-
C
vO2
venous oxygen content
- Hb
haemoglobin
- HR
heart rate
- Hct
hematocrit
- nHill
Hill coefficient
- O2
standard oxygen consumption
-
P
aCO2
arterial partial pressure of carbon dioxide
-
P
aO2
arterial partial pressure of oxygen
-
P
vO2
oxygen partial pressure in mixed venous blood
- P50
oxygen tension at half saturation of haemoglobin
-
P
VA, P
DA
blood pressure in ventral and dorsal aorta
- pHa
arterial pH
-
PIO2, PEO2
oxygen partial pressure of inspired and expired water
-
PO2
oxygen partial pressure
-
cardiac output
- SEM
standard error of mean
- S.I.D.
strong ion difference
- SV
cardiac stroke volume
- TO2
gill oxygen transfer factor
- U
oxygen extraction coefficient
- VA
ventilatory amplitude
- VF
ventilatory frequency
- VRG, VRS
branchial and systemic vascular resistances
-
ventilatory flow
-
ventilatory oxygen convection requirement 相似文献
6.
Dielectric properties of human and horse hemoglobin were studied at frequencies ranging from 20 kc./sec. to 7 Mc./sec. The relative errors in the measurements were usually less than 10?3 even for mildly conducting solutions (10?3M KCl). The experimental setup allowed us variation and measurement of the degree of oxygenation of the protein and to determine its dielectric parameters. Our main conclusion is that it was not possible to find any variation of the dielectric increment for hemoglobin oxygenation levels of 25, 50, 75, and 100%, approximately. This result is at variance with some previous reports. We cannot give the reason for this discrepancy but discuss some possible explanations. The specific dielectric increment, Δεs/c, of human hemoglobin was shown to be significantly smaller than that of horse hemoglobin (0.28 against 0.32). This physical property is lowered with increasing ionic strength I: Δεs/c = 0.28 and 0.20 for I = 10?4 and 10?3, respectively (human protein). 相似文献
7.
B. Desrues B. Collet M. P. Ramé D. Bourel P. Bourguet A. Martin P. Delaval L. Toujas L. Dazord 《Cancer immunology, immunotherapy : CII》1989,30(5):295-299
Monoclonal antibody Po66, produced by immunization against a patient's lung squamous cell carcinoma was found suitable for the scintigraphic detection of human tumours. Surprisingly, the cellular antigen recognized by Po66 was abundant in the cytoplasm of tumour cells but could not be detected on the surface membrane. In the present work the biodistribution of radiolabelled Po66 and of an unrelated immunoglobulin were studied comparatively after intravenous injection into nude mice bearing lung squamous cell carcinoma grafts. Radioactivity distribution among mouse organs and tumour was analysed by gamma counting and autohistoradiography. After injection, radiolabelled Po66 decreased rapidly from the blood in tumour-bearing animals whereas, in controls, it remained at a level comparable to that of the unrelated immunoglobulin. The antibody seemed slowly trapped by the tumour and, 12 days after its injection, distribution ratios between tumour and mouse organs reached values of 20-30 as against 1 in animals injected with the non-specific immunoglobulin. Autohistoradiographic investigations in the tumour confirmed the slow diffusion rate of the antibody, which remained in the vascular spaces up to the 24th hour after injection and diffused afterwards throughout the clusters of tumor cells. Furthermore, radioactivity was detected in cells which, unexpectedly, seemed morphologically unaltered. These cells, the viability of which remains to be determined, were predominant in the central area of the tumours. The results presented constitute new evidence of the ability of an in vivo injected monoclonal antibody to reach a cytoplasmic target inside non-necrotic cells and suggest that the cells permeable to the antibody might be in defective nutritional conditions. 相似文献
8.
Valérie Maxime Marguerite Peyraud-Waitzenergger Guy Claireaux Claude Peyraud 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1990,160(1):31-39
Summary Oxygen consumption, gill ventilation, blood acid-base/ionic status and haemoglobin oxygen affinity were studied in seawater-adapted adult salmon (Salmo salar) during five weeks after transfer into fresh water. Freshwater exposure induced the following changes: Standard oxygen consumption (
) and ventilatory flow (
) decreased markedly during the first days after transfer, then decreased more gradually until a new steady-state was achieved at which
and
were about 80% and 56% of the control values, respectively. The marked increase in oxygen extraction coefficient (Ew
O
2) and the marked decrease in the oxygen convection requirement (
) were associated with a reduction in the partial pressure of carbon dioxide in arterial blood (Pa
CO
2), in spite of a decrease of both ventilatory flow and water CO2 capacitance. These results suggested that transfer into fresh water induced an increase in branchial diffusive conductance. A biphasic pattern was observed in the time-course of the changes in both plasma ion concentration and acid-base status. During the first 10 days, plasma Na+, K+, and Cl– concentrations fell abruptly, then more gradually. [Cl–] decreased more than [Na+] resulting in a progressive increase in the [Na+]/[Cl–] ratio. During the second phase of acclimation to fresh water plasma Na+, K+, and Cl– concentrations progressively increased. [Cl–] increased more than [Na+], so that [Na+]/[Cl–] ratio decreased. Transfer into fresh water did not significantly change plasma lactate concentration. Upon exposure to fresh water, blood pH increased from 7.94±0.04 to 8.43±0.06 at day 10 and then decreased to 8.08±0.03 at day 34. The increase in blood pH induced by transfer to fresh water initially represented a mixed metabolic/respiratory alkalosis. However, after 15 days Pa
CO
2 had returned to pretransfer values and the alkalosis was purely metabolic. The metabolic component of the alkalosis was associated with appropriate changes in the plasma strong ion difference (S.I.D.). Blood alkalosis moved the oxygen dissociation curve to the left, so that P50 was decreased by 30% below the value in seawater for the maximal increase in blood pH. This rise in haemoglobin affinity for O2, associated with a marked increase in blood buffer capacity, are regarded as adaptative processes allowing the salmon to cope with the markedly increased energy expenditure required for upstream migration. 相似文献
9.
Juliette Gaëtan Sébastien Halary Maxime Millet Cécile Bernard Charlotte Duval Sahima Hamlaoui Amandine Hecquet Muriel Gugger Benjamin Marie Neha Mehta David Moreira Fériel Skouri-Panet Cynthia Travert Elodie Duprat Julie Leloup Karim Benzerara 《Environmental microbiology》2023,25(3):751-765
The formation of intracellular amorphous calcium carbonates (iACC) has been recently observed in a few cultured strains of Microcystis, a potentially toxic bloom-forming cyanobacterium found worldwide in freshwater ecosystems. If iACC-forming Microcystis are abundant within blooms, they may represent a significant amount of particulate Ca. Here, we investigate the significance of iACC biomineralization by Microcystis. First, the presence of iACC-forming Microcystis cells has been detected in several eutrophic lakes, indicating that this phenomenon occurs under environmental conditions. Second, some genotypic (presence/absence of ccyA, a marker gene of iACC biomineralization) and phenotypic (presence/absence of iACC) diversity have been detected within a collection of strains isolated from one single lake. This illustrates that this trait is frequent but also variable within Microcystis even at a single locality. Finally, one-third of publicly available genomes of Microcystis were shown to contain the ccyA gene, revealing a wide geographic and phylogenetic distribution within the genus. Overall, the present work shows that the formation of iACC by Microcystis is common under environmental conditions. While its biological function remains undetermined, this process should be further considered regarding the biology of Microcystis and implications on the Ca geochemical cycle in freshwater environments. 相似文献
10.
Martine de Boer Maaike te Lintel Hekkert Jiang Chang Bibi S. van Thiel Leonie Martens Maxime M. Bos Marion G. J. de Kleijnen Yanto Ridwan Yanti Octavia Elza D. van Deel Lau A. Blonden Renata M. C. Brandt Sander Barnhoorn Paula K. Bautista-Niño Ilona Krabbendam-Peters Rianne Wolswinkel Banafsheh Arshi Mohsen Ghanbari Christian Kupatt Leon J. de Windt A. H. Jan Danser Ingrid van der Pluijm Carol Ann Remme Monika Stoll Joris Pothof Anton J. M. Roks Maryam Kavousi Jeroen Essers Jolanda van der Velden Jan H. J. Hoeijmakers Dirk J. Duncker 《Aging cell》2023,22(3):e13768