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101.
Kar S Patel MA Tripathy RK Bajaj P Suvarnakar UV Pande AH 《Biochimica et biophysica acta》2012,1821(9):1200-1210
High density lipoprotein (HDL) particles are made up of lipid and protein constituents and apolipoprotein A-I (apoA-I) is a principal protein component that facilitates various biological activities of HDL particles. Increase in Ox-PL content of HDL particles makes them 'dysfunctional' and such modified HDL particles not only lose their athero-protective properties but also acquire pro-atherogenic and pro-inflammatory functions. The details of Ox-PL-induced alteration in the molecular properties of HDL particles are not clear. Paraoxonase 1 (PON1) is an HDL-associated enzyme that possesses anti-inflammatory and anti-atherogenic properties; and many of the athero-protective functions of HDL are attributed to the associated PON1. In this study we have characterized the physicochemical properties of reconstituted HDL (rHDL) particles containing varying amounts of Ox-PL and have compared their PON1 stimulation capacity. Our results show that increased Ox-PL content (a) modifies the physicochemical properties of the lipid domain of the rHDL particles, (b) decreases the stability and alters the conformation as well as orientation of apoA-I molecules on the rHDL particles, and (c) decreases the PON1 stimulation capacity of the rHDL particles. Our data indicate that the presence of Ox-PLs destabilizes the structure of the HDL particles and modifies their function. 相似文献
102.
Oubrie A Kaptein A de Zwart E Hoogenboom N Goorden R van de Kar B van Hoek M de Kimpe V van der Heijden R Borsboom J Kazemier B de Roos J Scheffers M Lommerse J Schultz-Fademrecht C Barf T 《Bioorganic & medicinal chemistry letters》2012,22(1):613-618
Optimization of our previously described pyrrolopiperidone series led to the identification of a new benzamide sub-series, which exhibits consistently high potency in biochemical and cell-based assays throughout the series. Strong inhibition of LPS-induced production of the cytokine TNFα is coupled to the regulation of HSP27 phosphorylation, indicating that the observed cellular effects result from the inhibition of MK2. X-ray crystallographic and computational analyses provide a rationale for the high potency of the series. 相似文献
103.
104.
The status of E. coli K-12 as an exclusively non-invasive, non-pathogenic bacterium has almost been incontrovertible. Our recent finding that a mutation in one of its main architectural protein, HU, converts E. coli K-12 to an actively invasive form suggests that gaining host cell entry might be an expedient survival tactic for traditional commensals during certain altered host conditions. The mutant E. coli (SK3842) exhibits properties usually associated with pathogenic bacteria: host cell invasion, phagosomal disruption and intracellular replication. However, unlike the situation with some pathogens, internalized SK3842 imparts anti-apoptotic and cyto-protective effects rather than lethality on the host cell, both in vitro and in vivo. Here, we show that SK3842 also provides colonization resistance against other invasive pathogens--a trait not shared by the parental commensal strain. Thus, the altered lifestyle of SK3842 encompasses characteristics both from traditional pathogens as well as beneficial probiotic strains. 相似文献
105.
Kar UK Jiang J Champion CI Salehi S Srivastava M Sharma S Rabizadeh S Niazi K Kickhoefer V Rome LH Kelly KA 《PloS one》2012,7(7):e38553
Background
Modifications of adjuvants that induce cell-mediated over antibody-mediated immunity is desired for development of vaccines. Nanocapsules have been found to be viable adjuvants and are amenable to engineering for desired immune responses. We previously showed that natural nanocapsules called vaults can be genetically engineered to elicit Th1 immunity and protection from a mucosal bacterial infection. The purpose of our study was to characterize immunity produced in response to OVA within vault nanoparticles and compare it to another nanocarrier.Methodology and Principal Findings
We characterized immunity resulting from immunization with the model antigen, ovalbumin (OVA) encased in vault nanocapsules and liposomes. We measured OVA responsive CD8+ and CD4+ memory T cell responses, cytokine production and antibody titers in vitro and in vivo. We found that immunization with OVA contain in vaults induced a greater number of anti-OVA CD8+ memory T cells and production of IFNγ plus CD4+ memory T cells. Also, modification of the vault body could change the immune response compared to OVA encased in liposomes.Conclusions/Significance
These experiments show that vault nanocapsules induced strong anti-OVA CD8+ and CD4+ T cell memory responses and modest antibody production, which markedly differed from the immune response induced by liposomes. We also found that the vault nanocapsule could be modified to change antibody isotypes in vivo. Thus it is possible to create a vault nanocapsule vaccine that can result in the unique combination of immunogen-responsive CD8+ and CD4+ T cell immunity coupled with an IgG1 response for future development of vault nanocapsule-based vaccines against antigens for human pathogens and cancer. 相似文献106.
Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O(2) (?-)) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O(2)(?-) and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O(2)(?-) and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O(2)(?-) and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(?-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(?-) and peroxynitrite concentration in the lumen. The increased O(2) (?-) and peroxynitrite can cause leukocytes priming through peroxynitrite and leukocytes activation through secondary stimuli of O(2)(?-) in bloodstream without endothelial interaction. This finding supports that leukocyte rolling/adhesion and activation are independent events. 相似文献
107.
108.
Van Eck M Hoekstra M Out R Bos IS Kruijt JK Hildebrand RB Van Berkel TJ 《Journal of lipid research》2008,49(1):136-146
Scavenger receptor class B type I (SR-BI) functions as an HDL receptor that promotes the selective uptake of cholesteryl esters (CEs). The physiological role of SR-BI in VLDL metabolism, however, is largely unknown. SR-BI deficiency resulted in elevated VLDL cholesterol levels, both on chow diet and upon challenge with high-cholesterol diets. To specifically elucidate the role of SR-BI in VLDL metabolism, the plasma clearance and hepatic uptake of (125)I-beta-VLDL were studied in SR-BI(+/+) and SR-BI(-/-) mice. At 20 min after injection, 66 +/- 2% of the injected dose was taken up by the liver in SR-BI(+/+) mice, as compared with only 22 +/- 4% (P = 0.0007) in SR-BI(-/-) mice. In vitro studies established that the B(max) of (125)I-beta-VLDL binding was reduced from 469 +/- 30 ng/mg in SR-BI(+/+) hepatocytes to 305 +/- 20 ng/mg (P = 0.01) in SR-BI(-/-) hepatocytes. Both in vivo and in vitro, limited to no selective uptake of CEs from beta-VLDL was found. Interestingly, HDL effectively competed for the association of beta-VLDL in the presence as well as in the absence of SR-BI, indicating a second common recognition site. In conclusion, SR-BI plays an important physiological role in the metabolism of VLDL (remnants). 相似文献
109.
Catalase plays a central role in plant stress responses but is highly susceptible to photoinhibition. A rice catalase-B protein
avoiding photoinhibition was developed by mutagenesis of specific amino acids: Leu-189 to Trp-189 and His-225 to Thr-225 and
then recombinantly expressed in E. coli. In addition, the site specific mutation also induced 2–2.5-fold increase in enzyme velocity with high affinity for its substrate
and showed nearly a 3-fold lower K
m
than the wild protein. These characteristic of mutated rice catalase-B is highly promising in transgenic research to increase
plant productivity under stress conditions. 相似文献
110.
The aim of this study was to investigate the Helicobacter pylori (Hp) status of patients who underwent successful eradication therapy 1 year prior to the study and to evaluate their current symptoms. METHODS: all of the patients were initially evaluated by oesophago-gastro-bulboscopy and the Hp status was determined by at least two different methods [rapid urease test, histology or urea breath test (UBT)]. The Hp infection was treated with a 1-week triple therapy protocol, and the UBT was repeated 4-6 weeks later. We invited back 110 patients who had negative post-eradication UBT results 12+/-3 months prior to the study period. UBT was repeated and a questionnaire was completed about the previous and present complaints and medication. RESULTS: 80 of the 110 patients (73%) came back for the follow-up. Twenty five patients had peptic ulcer disease, 36 patients had gastritis or duodenitis without erosive lesions, and 19 patients had erosive form of gastritis or duodenitis initially. All of the patients except one in the erosive gastritis group had negative control UBT 1 year after the eradication, which means 1.25% recurrence rate within 1 year. The eradication therapy completely revealed the symptoms of 16 patients in the ulcer group (64%), 13 patients in the gastroduodenitis group (36%, P=0.03 vs. ulcer patients), 10 patients with erosive gastroduodenitis (52%), but this was only temporary. One year after the eradication therapy seven of the ulcer patients (28%), 11 patients with gastroduodenitis (31%) and seven patients with erosive gastroduodenitis (37%) were symptom-free. Most of the patients had epigastric pain (44%), heartburn (43%) and/or abdominal distension (33%). Nine ulcer patients (36%), 10 patients with gastroduodenitis (28%) and five patients with erosive gastroduodenitis (26%) were taking H(2)-blockers regularly. CONCLUSION: the 1-month post-eradication UBT was probable true negative in all of the evaluated cases, since 79 patients (98.75%) were also negative after 1 year. The Hp recurrence rate is very low (1.25%) in a 1-year period. The symptoms were relieved shortly after eradication therapy in the majority of patients with ulcer disease or erosive lesions. However, significantly smaller portion of the patients with gastroduodenitis became symptom-free. Only about one third of the treated patients remained symptom-free 1 year after the eradication. 相似文献