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Véronique Pons Nizar Serhan Stéphanie Gayral Camille Malaval Michel Nauze Nicole Malet Muriel Laffargue Céline Galés Laurent O. Martinez 《Cellular and molecular life sciences : CMLS》2014,71(9):1775-1788
The protective effect of high density lipoproteins (HDL) against atherosclerosis is mainly attributed to their capacity to transport excess cholesterol from peripheral tissues back to the liver for further elimination into the bile, a process called reverse cholesterol transport (RCT). Recently, the importance of the P2Y13 receptor (P2Y13-R) was highlighted in HDL metabolism since HDL uptake by the liver was decreased in P2Y13-R deficient mice, which translated into impaired RCT. Here, we investigated for the first time the molecular mechanisms regulating cell surface expression of P2Y13-R. When transiently expressed, P2Y13-R was mainly detected in the endoplasmic reticulum (ER) and strongly subjected to proteasome degradation while its homologous P2Y12 receptor (P2Y12-R) was efficiently targeted to the plasma membrane. We observed an inverse correlation between cell surface expression and ubiquitination level of P2Y13-R in the ER, suggesting a close link between ubiquitination of P2Y13-R and its efficient targeting to the plasma membrane. The C-terminus tail exchange between P2Y13-R and P2Y12-R strongly restored plasma membrane expression of P2Y13-R, suggesting the involvement of the intra-cytoplasmic tail of P2Y13-R in expression defect. Accordingly, proteasomal inhibition increased plasma membrane expression of functionally active P2Y13-R in hepatocytes, and consequently stimulated P2Y13-R-mediated HDL endocytosis. Importantly, proteasomal inhibition strongly potentiated HDL hepatic uptake (>200 %) in wild-type but not in P2Y13-R-deficient mice, thus reinforcing the role of P2Y13-R expression in regulating HDL metabolism. Therefore, specific inhibition of the ubiquitin–proteasome system might be a novel powerful HDL therapy to enhance P2Y13-R expression and consequently promote the overall RCT. 相似文献
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L Feliubadaló M Font J Purroy F Rousaud X Estivill V Nunes E Golomb M Centola I Aksentijevich Y Kreiss B Goldman M Pras D L Kastner E Pras P Gasparini L Bisceglia E Beccia M Gallucci L de Sanctis A Ponzone G F Rizzoni L Zelante M T Bassi A L George M Manzoni A De Grandi M Riboni J K Endsley A Ballabio G Borsani N Reig E Fernández R Estévez M Pineda D Torrents M Camps J Lloberas A Zorzano M Palacín 《Nature genetics》1999,23(1):52-57
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Wójcik C 《Cellular and molecular life sciences : CMLS》1999,56(11-12):908-917
The proteasome (multicatalytic proteinase complex, prosome) is a major cytoplasmic proteolytic enzyme, responsible for degradation of the vast majority of intracellular proteins. Proteins degraded by the proteasome are usually tagged with multiple ubiquitin moieties, conjugated to the substrates by a complicated cascade of enzymes. Over the last years, evidence has accumulated that changes in the expression and activity of the different components of the ubiquitin-proteasome system occur during apoptosis. Proteasome inhibitors have been used to induce apoptosis in various cell types, whereas in others, these compounds were able to prevent apoptosis induced by different stimuli. The proteasome mediated step(s) in apoptosis is located upstream of mitochondrial changes and caspase activation, and can involve in different systems Bcl-2, Jun N-terminal kinase, heat shock proteins, Myc, p53, polyamines and other factors. 相似文献
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F. J. Oliver M. K. L. Collins A. López-Rivas 《Cellular and molecular life sciences : CMLS》1996,52(10-11):995-1000
Fidelity in DNA synthesis and repair is largely dependent on a balanced supply of deoxynucleotide triphosphate (dNTP) pools. Results from different groups have shown that alterations in dNTP supply result in DNA fragmentation and cell death with characteristics of apoptosis. We have recently shown that in apoptosis driven by deprivation of interleukin-3 (IL-3) in a murine hemopoietic cell line, there is a rapid imbalance in the availability of dNTP that precedes DNA fragmentation. In these cells, dNTP pool balance is closely coupled to the function of the salvage pathway of dNTP synthesis. Apoptosis, induced by treatment of these cells with drugs that inhibit the de novo dNTP synthesis, is prevented when dNTP precursors are supplied through the salvage pathway. IL-3 regulates thymidine kinase activity, suggesting that alterations in dNTP metabolism after IL-3 deprivation could be a relevant event in the commitment of hemopoietic cells to apoptosis. 相似文献
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Properties of granules that contain kallikrein and renin 总被引:1,自引:0,他引:1
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S. Tóth L. Muszbek T. Szilágyi J. Laczkó 《Cellular and molecular life sciences : CMLS》1969,25(10):1085-1086
Zusammenfassung Kasein, Pepton bzw. Baktokasiton wurde als präparierende Erstinjektion für lokalisiertes Shwartzman-Phänomen an Kaninchen verwendet. Nach provozierender i.v. Endotoxininjektion kommt es zum typischen Shwartzman-Phänomen. Da die verwendeten Substanzen Chemotaxis von Leukozyten verursachen, ist anzunehmen, dass die an Stelle der präparierenden Injektion angesammelten Leukozyten in der Ausbildung des Shwartzman-Phänomens eine vorwiegende Rolle spielen. 相似文献