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51.
Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores. 总被引:26,自引:0,他引:26
Leta K Nutt Abujiang Pataer Jessica Pahler Bingliang Fang Jack Roth David J McConkey Stephen G Swisher 《The Journal of biological chemistry》2002,277(11):9219-9225
Alterations in intracellular Ca(2+) homeostasis and cytochrome c release from mitochondria have been implicated in the regulation of apoptosis, but the relationship between these events remains unclear. Here we report that enforced expression of either Bax or Bak via adenoviral gene delivery results in the accumulation of the proteins in the endoplasmic reticulum (ER) and mitochondria, resulting in early caspase-independent BCL-2-sensitive release of the ER Ca(2+) pool and subsequent Ca(2+) accumulation in mitochondria. The inhibition of ER-to-mitochondrial Ca(2+) transport with a specific inhibitor of mitochondrial Ca(2+) uptake attenuates cytochrome c release and downstream biochemical events associated with apoptosis. Bax and Bak also directly sensitize mitochondria to cytochrome c release induced by immediate emptying of ER Ca(2+) pool. Our results demonstrate that the effects of the "multidomain" proapoptotic BCL-2 family members Bak and Bax involve direct effects on the endoplasmic reticular Ca(2+) pool with subsequent sensitization of mitochondria to calcium-mediated fluxes and cytochrome c release. These effects modulate the kinetics of cytochrome c release and apoptosis. 相似文献
52.
Nucleolar protein metabolism in actinomycin D treated HeLa cells 总被引:2,自引:0,他引:2
53.
Eoghan de Barra Susanne H. Hodgson Katie J. Ewer Carly M. Bliss Kerrie Hennigan Ann Collins Eleanor Berrie Alison M. Lawrie Sarah C. Gilbert Alfredo Nicosia Samuel J. McConkey Adrian V. S. Hill 《PloS one》2014,9(12)
Background
Plasmodium falciparum (P. falciparum) malaria remains a significant cause of mortality and morbidity throughout the world. Development of an effective vaccine would be a key intervention to reduce the considerable social and economic impact of malaria.Methodology
We conducted a Phase Ia, non-randomized, clinical trial in 24 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding the circumsporozoite protein (CS) of P. falciparum.Results
ChAd63-MVA CS administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to CS. With a priming ChAd63 CS dose of 5×109 vp responses peaked at a mean of 1947 SFC/million PBMC (median 1524) measured by ELIspot 7 days after the MVA boost and showed a mixed CD4+/CD8+ phenotype. With a higher priming dose of ChAd63 CS dose 5×1010 vp T cell responses did not increase (mean 1659 SFC/million PBMC, median 1049). Serum IgG responses to CS were modest and peaked at day 14 post ChAd63 CS (median antibody concentration for all groups at day 14 of 1.3 µg/ml (range 0–11.9), but persisted throughout late follow-up (day 140 median antibody concentration groups 1B & 2B 0.9 µg/ml (range 0–4.7).Conclusions
ChAd63-MVA is a safe and highly immunogenic delivery platform for the CS antigen in humans which warrants efficacy testing.Trial Registration
ClinicalTrials.gov NCT01450280相似文献54.
55.
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57.
Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides 总被引:2,自引:0,他引:2
Background
The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.Results
EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.Conclusion
DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress. 相似文献58.
Zhenyu Cheng Owen Z. Woody Jiming Song Bernard R. Glick Brendan J. McConkey 《Proteomics》2009,9(17):4271-4274
A proteome reference map containing 326 2‐D gel spots representing 275 different proteins was constructed for the plant growth‐promoting bacterium Pseudomonas putida UW4. Protein identifications were obtained using Q‐TOF MS/MS spectra matching to homologous proteins from other Pseudomonas strains and confirmed by PMF analysis. This data set is accessible at http://world‐2dpage.expasy.org/repository/ and will aid in further characterization of Pseudomonas strains and interactions of plant growth‐promoting bacterium with the plant rhizosphere environment. 相似文献
59.
JÉRÔME SUEUR SOLÈNE JANIQUE CAROLINE SIMONIS JAMES F. C. WINDMILL MICHEL BAYLAC 《Biological journal of the Linnean Society. Linnean Society of London》2010,101(4):922-934
Many insect species rely on their sense of audition to find a mate, to localize prey or to escape from a predator. Cicadas are particularly known for their loud call and the conspicuous tympanal hearing system located in their abdomen. The vibration pattern of the tympanal membrane (TM) has been investigated recently revealing mechanical properties specific to species and sex. Although TM size and shape is likely to affect these patterns, the geometry of the cicada ear has never been examined per se. Focusing on three Mediterranean cicada species, namely Cicadatra atra, Cicada orni and Lyristes plebejus, we investigated the structure of TM shape variation at two levels, within and across species. Applying an elliptic Fourier analysis to the outlines of both male and female TMs, we estimated sexual dimorphism and species effects. Cicadatra atra showed a large TM compared with its small size, probably as a result of selective constraints related to the role of the TM in sound production. Sexual dimorphism seemed to be greater than interspecific variation, indicating that constraints operating on sex might be more selective than those acting on species identification. In addition, C. orni appeared to be significantly different from the two other species. This morphological peculiarity could be related to the unique vibrational pattern of its membrane. This would establish for the first time a direct link between the shape and mechanism of a hearing organ. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101 , 922–934. 相似文献
60.
A Luquita L Urli MJ Svetaz AM Gennaro ME Giorgetti G Pistone R Volpintesta S Palatnik M Rasia 《Journal of biomedical science》2010,17(1):8