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1.
Motohiro Sekiya Yoshiaki Tamura Masaki Igarashi Mikio Takanashi Satoru Takase Yoshinori Takeuchi Midori Kubota Yoko Iizuka Takanari Gotoda Hitoshi Shimano Takashi Kadowaki Shun Ishibashi 《Biochemical and biophysical research communications》2009,387(3):511-515
It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic β-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lepob/ob/HSL−/−) and explored the role of HSL in pancreatic β-cells in the setting of obesity. Lepob/ob/HSL−/− developed elevated blood glucose levels and reduced plasma insulin levels compared with Lepob/ob/HSL+/+ in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep+/+ background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lepob/ob islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lepob/ob mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity. 相似文献
2.
Adam M. Lopez Kenneth S. Posey Stephen D. Turley 《Biochemical and biophysical research communications》2014
Sterol O-acyltransferase 2 (SOAT2), also known as ACAT2, is the major cholesterol esterifying enzyme in the liver and small intestine (SI). Esterified cholesterol (EC) carried in certain classes of plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease (WD) or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to what effect the loss of SOAT2 function might have on tissue EC sequestration in LAL-deficient mice. When weaned at 21 days, Lal−/−:Soat2+/+ mice had a whole liver cholesterol content (mg/organ) of 24.7 mg vs 1.9 mg in Lal+/+:Soat2+/+ littermates, with almost all the excess sterol being esterified. Over the next 31 days, liver cholesterol content in the Lal−/−:Soat2+/+ mice increased to 145 ± 2 mg but to only 29 ± 2 mg in their Lal−/−:Soat2−/− littermates. The level of EC accumulation in the SI of the Lal−/−:Soat2−/− mice was also much less than in their Lal−/−:Soat2+/+ littermates. In addition, there was a >70% reduction in plasma transaminase activities in the Lal−/−:Soat2−/− mice. These studies illustrate how the severity of disease in a mouse model for CESD can be substantially ameliorated by elimination of SOAT2 function. 相似文献
3.
A recombination proficient strain ofEscherichia coli which is recB? recC? sbcB? has been subjected to mutagenesis by nitrosoguanidine. Among the recombination deficient mutants isolated one was sbcB+, three were recA~ and 11 were mutants in at least four newrec genes: recF, recJ, recK and recL. recF143 and recL152 are cotransducible with ilv but they lie on opposite sides of the ilv operons as determined by Fstudies. recF, recL and recK are not involved in the RecBC pathway of recombination since a recB+recC+sbcB? strain carrying a mutation in one of these genes is recombination proficient. Hence the hypothesis that a RecF pathway of recombination can operate as a partially independent substitute for the RecBC pathway of recombination is supported. recF?recB+ and recF+recB? single mutants are sensitive to u.v. irradiation while the recF?recB? double mutant is more sensitive than either single mutant. The sensitivity of the recB?recC?sbcB?recF? strain approaches the sensitivity of a recA? single mutant. This is interpreted to mean that there are partially independent RecF and RecBC pathways for the repair of u.v. damage. recJ and mutations were not mapped precisely; hence the mutant properties they confer can not be stated conclusively. 相似文献
4.
The asymmetrical nitrosyl-deoxy hybrid haemoglobin, (αNOβNO), (αdeoxyβdeoxy), was prepared by removing oxygen with sodium dithionite from a mixture of oxyhaemoglobin and nitrosylhaemoglobin (Cassoly, 1978). This asymmetrical hybrid exhibited a distinctive triplet hyperfine structure in the electron paramagnetic resonance spectrum. This triplet has been shown to arise predominantly from the nitrosyl haem of an α subunit which has a deoxy-like structure (Nagai et al., 1978). By removing one or two carboxyl-terminal residues by carboxypeptidase digestion before mixing, one can obtain asymmetrical nitrosyl-deoxy hybrid haemoglobins in which only one of the four subunits is specifically modified. Eight such modified derivatives were examined by e.p.r.2. They were (desArgαNOβNO) (αdeoxyβdeoxy), (desArg-TyrαNOβNO) (αdeoxyβdeoxy), (αNOdesHisβNO) (αdeoxyβdeoxy), (αNOdesHis-Tyr βNO) (αdeoxyβdeoxy), (αNOβNO) (desArgαdeoxyβdeoxy), (αNOβNO) (desArg-Tyrαdeoxyβdeoxy), (αNOβNO) (αdeoxydesHisβdeoxy) and (αNOβNO) (αdeoxydesHis-Tyrβdeoxy), where desArg, desArg-Tyr, desHis and desHis-Tyr indicate that the amino acids were removed from the carboxyl terminus of the subunit.The e.p.r. spectra for these eight derivatives have a more or less reduced relative intensity of the triplet, indicating that the non-covalent bonds involving carboxyl-terminal residues which stabilize the structure of deoxyhaemoglobin (Perutz, 1970) must all be intact in the unmodified asymmetrical nitrosyl-deoxy hybrid haemoglobin, (αNOβNO) (αdeoxyβdeoxy). By comparing the relative intensity of the triplet we were able to examine the effect of modification of one specific carboxyl terminus on the nitrosyl haem in the α1 subunit. The effect was not symmetric, but increased in the order α1 < β2 < β1 < α1 (suffices 1 and 2 as defined by Perutz (1965)). We attribute this order to the non-equivalence of intersubunit interactions. 相似文献
5.
6.
Clarke and Carbon's collection of 2000 E. coli strains, which harbor ColE1 plasmids carrying small random segments of the E. coli chromosome, was screened for the correction of thermosensitive defects in the processes of cell division and in the synthesis of murein-lipoprotein. The genetic defects examined in this screening were those in partition of daughter nuclei (par), cleavage of cells (fts), determination of a cell shape (rod), and synthesis of murein-lipoprotein (lpo). We found plasmids carrying E. coli chromosomal segments containing ftsB+, ftsE+,ftsI+,ftsM+, and parA+. However, none was found to transfer ftsA+, ftsC+, ftsF+, ftsG+, ftsJ+, ftsK+, ftsL+, parB+, rod+, and lpo+. One of the donor strains transferring a gene that corrected thermosensitive cell cleavage in the ftsI? mutant overproduced the penicillin-binding protein 3 by ca. 10-fold. 相似文献
7.
Kei Sasaoka Tadashi Ogawa Masumi Kimoto 《Archives of biochemistry and biophysics》1982,219(2):454-458
Ninhydrin-negative conjugates of basic amino acids were isolated from rat urine and were characterized. The following conjugates of basic amino acids are the compounds newly identified in animal urine specimens, Nα-acetyl-Nπ-methylhistidine, Nα-(N-acetyl-β-alanyl)histidine (N-acetylcarnosine), Nα-acetyl-NG,N′G-dimethylarginine, Nα-acetyl-NG,NG-dimethylarginine, and Nα-acetyl-N?,N?,N?-trimethyllysine. 相似文献
8.
Citrobacter freundii Hfr donor strains were isolated from a C. freundii strain harbouring a temperature-sensitive factor F ts 114 lac +, by selecting for integrative suppression of the ts 114 mutation. Three Hfr strains were characterized, which transfer their chromosomes in a linear and oriented order. The first strain transfers: O-aro +-ilv +-pur +-thr +-leu +-pro +, the second: O-ilv +-pur +-thr +-leu +-pro + and the third: O-ilv +-aro +-nad +-his +-pro +. The whole chromosome is transferred into the recipient cell within about 145 minutes. From these results we concluded that the linkage map of C. freundii is circular. Mating-pair formation on a membrane filter resulted in more recombinants being formed as compared with mating-pair formation in liquid medium. Furthermore the mating-pairs formed on a membrane were more stable. From one Hfr strain heterogenic F-prime factors could be isolated bearing the F ts 114 lac + genes from Escherichia coli and the pur + and/or ilv + genes from C. freundii. Preliminary mapping by interrupted mating indicated that the linkage map of C. freundii is in general very similar to those of E. coli, Salmonella typhimurium and Klebsiella aerogenes. 相似文献
9.
A chiral spin crossover iron(II) complex, fac-Λ-[FeII(HLR)3](ClO4)2·EtOH was synthesized and its crystal structures in both the high-spin (HS) and low-spin (LS) states were determined, where HLR denotes 2-methylimidazol-4-yl-methylideneamino-R-(+)-1-methylphenyl. The complex assumes octahedral coordination geometry of N6 donor atoms by three bidentate ligands HLR. The complex exists as the facial-Λ-isomer of fac-Λ-[FeII(HLR)3]2+ of the possible geometrical fac- and mer-isomers and the Δ- and Λ-enantiomorphs. The X-ray structural analyses revealed that the R-form of the ligand (HLR) induces the fac-Λ-isomer of fac-Λ-[FeII(HLR)3]2+ and the S-form of the ligand (HLS) induces the fac-Δ-isomer of fac-Δ-[Fe(HLS)3]2+. The complex fac-Λ-[FeII(HLR)3](ClO4)2·EtOH shows a complete steep spin crossover between the HS and the LS states at T1/2 = 195 K. 相似文献
10.
Hydrochlorothiazide (HCTZ) was shown to inhibit the transepithelial NaCl transport and the apical Na+-Cl? symport and to depolarize the apical membrane potential in the rabbit gallbladder epithelium. The depolarization was likely related to the opening of a Cl? conductance. To better understand whether an apical Cl? leak is involved in the mechanism of action of HCTZ, the transapical Cl? backflux was measured radiochemically by the washout technique. The gallbladder wall, pretreated with pronase on the serosal side to homogenize the subepithelium, was loaded with 36Cl? on the luminal side; mucosal and serosal 36Cl? effluxes (J m , J s ) were then measured every 2 min. The pretreatment with pronase did not alter the membrane potentials and the selectivity of the epithelium. Under control conditions and the tissue in steady-state, J m and J s time courses were each described by two exponential decays (A,B); the rate constants, k A and k B , were 0.71 ±0.03 and 0.16±0.01 min?1, respectively, and correspondingly the half-times (t 1 2A , t 1 2B ) were 1.01±0.05 and 5.00±0.44 min (n=10); these parameters were not significantly different for J m and J s time courses. J s was always greater than J m (J s /J m =2.02±0.22 and 1.43 ±0.17 for A and B decays). Under SCN? treatment in steady-state conditions, both J m and J s time courses were described by only one exponential decay, the component B being abolished. Moreover t 1 2A was similar to that predictable for the subepithelium. It follows that it is the component B which exits the epithelial compartment. Based on the intracellular specific activity and 36Cl? J m B at 0 min time of the washout experiment, the cell-lumen Cl? backflux in steady-state was calculated to be equal to about 2 μmol cm?2hr?1, in agreement with the value indirectly computable by other techniques. The experimental model was well responsive to different external challenges (increases in media osmolalities; luminal treatment with nystatin). HCTZ (2.5 · 10?4 m) largely increased 36Cl? J m B . The increase was abolished by luminal treatment with 10?4 m SITS, which not only brought back the efflux time courses to the ones observed under control conditions but even increased J s /J m of the cellular component, an indication of a reduced J m B . It is concluded that HCTZ opens an apical, SITS-sensitive Cl? leak, which contributes to dissipate the intracellular Cl? accumulation and to inhibit the NaCl transepithelial transport. Moreover, the drug is likely to reduce the basal electroneutral Cl? backflux supported by Na+-Cl? cotransport, in agreement with the inhibition of the cotransport itself. 相似文献
11.
A new method for the simple analysis of methylated amino acids based on autoradiography is introduced. With this technique a survey of protein methylation in a prokaryote, Escherichia coli, and a eukaryote, fibroblasts in culture, was carried out in an attempt to identify, quantitate, and determine the subcellular localization of all the methylated amino acids found in the proteins of these organisms.In mammalian cells using an established mouse fibroblast line (3T3), we have found that nuclei-free and mitochondria-free cytoplasm contain readily detectable amounts of four identifiable methylated amino acids: N?,N?-dimethyllysine, N?,N?,N?-trimethyllysine, NG,NG-dimethylarginine (or NG-methylarginine), and NG,N′G-dimethylarginine. The crude nuclear pellet also contains these methylated amino acids, but in addition contains N?-methyllysine and a new as yet unidentified methylated compound. Histones purified from these nuclei contain essentially the same array of methylated compounds.The ribosomal subunits of the mammalian cells contained only small amounts of the methylated amino acids; the 40S subunit contained a substantial amount of just one, NG,NG-dimethylarginine (or NG-methylarginine), and smaller amounts of NG,N′G-dimethylarginine, and an as yet unidentified methylated compound. The 60S subunit contained even smaller amounts of methylated amino acids, 50% of which was N?,N?,N?-trimethyllysine and smaller amounts of N?-methyllysine, N?,N?-dimethyllysine, and NG,NG-dimethylarginine. These subunits also contained an as yet unidentified methylated compoundThese results were in marked contrast to those that we obtained with the prokaryote, Escherichia coli. Only the proteins of the 50S ribosomal subunit of the bacteria contained methylated amino acids. Of those present 50% was N?,N?,N?-trimethyllysine, with the remainder distributed about equally between N?-methyllysine and three unknowns, one of which is apparently the same as that found in the 60S subunit of the mouse fibroblasts. All of the N?-methyllysine was apparently in the small acidic proteins, L7 and L12. 相似文献
12.
K.T. Shanmugam Arnold S. Loo R.C. Valentine 《Biochimica et Biophysica Acta (BBA)/General Subjects》1974,338(2):545-553
Deletions of the nitrogen fixation (nif) region of the Klebsiella genome were isolated by selecting for resistance to virulent phages whose resistance loci are adjacent to nif. The extent of the various deletions was monitored by assaying several different enzymes or gene products coded for by this segment of DNA. Three classes of deletion mutants were detected: (1) gluconate-6-phosphate dehydrogenase minus (gnd?), histidine minus but histidinol dehydrogenase plus (his?, his D+), nitrogenase plus (nif+), shikimate utilization plus (shu+); (2) gnd?, his D?, nif?, shu+; (3) gnd?, his D?, nif?, shu?. From these studies we conclude that the cluster of nif genes essential for nitrogenase activity is located on the genetic linkage map of Klebsiella between his and shu; the gene order in this region in thus phage-resistance locus (rfb?), gnd, his operon, nif, shu. Genetic analysis substantiates the finding that the nif cluster is located proximally to the operator end of the his operon. 相似文献
13.
Tero Huhtiniemi Tiina Suuronen Maija Lahtela-Kakkonen Tanja Bruijn Sanna Jääskeläinen Antti Poso Antero Salminen Jukka Leppänen Elina Jarho 《Bioorganic & medicinal chemistry》2010,18(15):5616-5625
Sirtuins catalyze the NAD+ dependent deacetylation of Nε-acetyl lysine residues to nicotinamide, O′-acetyl-ADP-ribose (OAADPR) and Nε-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel Nε-modified lysine containing inhibitors against SIRT1 and SIRT2. Nε-Selenoacetyl and Nε-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied Nε-thioacetyl group. The Nε-3,3-dimethylacryl and Nε-isovaleryl moieties gave significant inhibition in comparison to the Nε-acetyl group present in the substrates. In addition, the studied Nε-alkanoyl, Nε-α,β-unsaturated carbonyl and Nε-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the Nε-modification. These results are applicable for further screening of Nε-acetyl analogues. 相似文献
14.
Donor Strains of the Soft-Rot Bacterium Erwinia chrysanthemi and Conjugational Transfer of the Pectolytic Capacity 总被引:22,自引:16,他引:6
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Donor strains of Erwinia chrysanthemi ICPB EC16, a member of the soft-rot (pectolytic) section of the enterobacterial genus Erwinia, were obtained by chromosomal integration of an F′lac+ plasmid originating from Escherichia coli. These stable donor strains, selected from an unstable F′lac+ heterogenote by repeated platings of single Lac+ colonies on lactose minimal agar, do not segregate (as does the parent F′lac+ heterogenote) into Lac− or F− clones, in either the presence or absence of acridine orange. One representative donor strain (from the 12 that have been selected) has been examined in more detail; it can transfer ade+, gal+, gtu+ (utilization of galacturonate), his+, lac+, leu+, lys+, mcu+ (multiple carbohydrate utilization), pat+ (production of polygalacturonic acid trans-eliminase), thr+, and trp+ in a polarized manner to appropriate recipient strains of E. chrysanthemi; the frequencies of ade+, leu+, and thr+ transfer were higher than those of the other markers tested to date. This donor strain transfers lac+ genes during a 6-h mating on membranes; most of the Lac+ recombinants are donors of chromosomal markers. The kinetics of entry as well as the frequencies of transfer of chromosomal markers indicate that thr+ and leu+ enter the recipient as proximal markers and that lac+ enters as a distal marker. Analysis of the recombinants demonstrates close linkage between thr and leu, ade and thr, his and pat, and his and trp loci. The results suggest that the integration of F′lac+ into the chromosome of E. chrysanthemi has occurred at a region adjacent to the leu-thr loci, and that the chromosome is transferred in the following sequence: origin----leu--thr--ade--lys--mcu--pat--his--trp--gal--gtu--lac--F. Plant-tissue maceration occurs in Pat+ recombinants and not in Pat− recombinants, even though both form another pectolytic enzyme, hydrolytic polygalacturonase. This genetic evidence supports the idea that the E. chrysanthemi polygalacturonic acid trans-eliminase plays an essential role in bringing about plant-tissue maceration. 相似文献
15.
Recombinant frequency was compared with nucleotide distance in crosses involving markers in either the PRM or the cy region of phage λ. For each pair of markers, we performed reciprocal four-factor crosses of the following types: (I) A+m1 +m2-B- x A-m1 -m2+B+; and (II) A+m1 -m2+B- x A-m1 +m2-B+. In crosses of type I, the frequency of A+m1 +m2+B+ recombinants among total (selected) A+B+ progeny was directly proportional to nucleotide distance between m1 and m2 in the range from 3 to 160 nucleotides. When less than three nucleotides separated m1 and m2, the measured yields of m1+m2+ recombinants were significantly depressed.
We also found that the frequency of A+m1 +m2+B+ recombinants among total A+B+ progeny was significantly lower (about 10-fold on the average) in crosses of type II than in the corresponding crosses of type I. Since mismatch correction should yield A+m1 +m2+B+ recombinants with approximately equal frequencies in type I and II crosses, we suggest: (1) that most m1+m2+ recombinants produced in type I crosses must arise from the formation of heteroduplex structures with a discontinuity (in the source of genetic information) between sites m1 and m2, and (2) that mismatch correction is not a major pathway for production of recombinants for close markers in normal λ infection.
相似文献16.
Analysis of the Sequence and Phenotype of Drosophila Sex combs reduced Alleles Reveals Potential Functions of Conserved Protein Motifs of the Sex combs reduced Protein
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The Drosophila Hox gene, Sex combs reduced (Scr), is required for patterning the larval and adult, labial and prothoracic segments. Fifteen Scr alleles were sequenced and the phenotypes analyzed in detail. Six null alleles were nonsense mutations (Scr2, Scr4, Scr11, Scr13, Scr13A, and Scr16) and one was an intragenic deletion (Scr17). Five hypomorphic alleles were missense mutations (Scr1, Scr3, Scr5, Scr6, and Scr8) and one was a small protein deletion (Scr15). Protein sequence changes were found in four of the five highly conserved domains of SCR: the DYTQL motif (Scr15), YPWM motif (Scr3), Homeodomain (Scr1), and C-terminal domain (CTD) (Scr6), indicating importance for SCR function. Analysis of the pleiotropy of viable Scr alleles for the formation of pseudotracheae suggests that the DYTQL motif and the CTD mediate a genetic interaction with proboscipedia. One allele Scr14, a missense allele in the conserved octapeptide, was an antimorphic allele that exhibited three interesting genetic properties. First, Scr14/Df had the same phenotype as Scr+/Df. Second, the ability of the Scr14 allele to interact intragenetically with Scr alleles mapped to the first 82 amino acids of SCR, which contains the octapeptide motif. Third, Scr6, which has two missense changes in the CTD, did not interact genetically with Scr14. 相似文献
17.
Jonathan M. White Victor W.L. Ng Paul D. Smith Michelle K. Taylor Charles G. Young 《Inorganica chimica acta》2009,362(12):4570-5792
Red-black [TpiPr∗MoVO]2(μ-O)(μ-MoVIO4) (1, TpiPr∗ = hydrobis(3-isopropylpyrazolyl)(5-isopropylpyrazolyl)borate) has been isolated as a by-product in the synthesis of NEt4[TpiPrMo(CO)3] (TpiPr = hydrotris(3-isopropylpyrazolyl)borate) and characterized by spectroscopic and X-ray crystallographic techniques. The trinuclear, mixed-valence complex contains two distorted octahedral anti-TpiPr∗MoVO centers bridged by bent oxo (Mo-O-Mo av. 158.7°) and tetrahedral κO,κO′-molybdate ligands. The complex contains a six-membered, non-planar Mo3(μ-O)3 core and two 1,2-borotropically-shifted TpiPr∗ ligands (with the shifted pyrazolyl trans to MoV=O). Aerial decomposition of solid NEt4[TpiPrMo(CO)3] produces sky-blue, diamagnetic TpiPrMoO(iPrpz)(iPrpzH) (2, iPrpz- = 3-isopropylpyrazolate, iPrpzH = 3-isopropyl-2H-pyrazole). Molecules of 2 feature a tridentate fac-TpiPr ligand and mutually cis terminal oxo (MoO = 1.665(2) Å) and monodentate iPrpz− and iPrpzH ligands. The latter are formed by B-N bond cleavage of TpiPr. The complex can also be synthesized by reacting NEt4[TpiPrMo(CO)3] with excess 3-isopropylpyrazole and dioxygen at 100 °C. Cleavage of the B-N bond(s) of TpiPr was also observed in the formation of TpiPrMoO(SPh)(iPrpzH) (3) as a by-product in the synthesis of TpiPrMoO2(SPh). In the monohydrate, 3 exhibits a distorted octahedral geometry defined by a tridentate fac-TpiPr ligand and mutually cis terminal oxo (MoO = 1.676(3) Å) and monodentate SPh− and iPrpzH ligands. The pyrazole β-NH group is observed to participate in a hydrogen-bond to the lattice water molecule. The complex can be synthesized in high yield by reducing TpiPrMoO2(SPh) by HSPh or PPh3 in the presence of excess 3-isopropylpyrazole. 相似文献
18.
O. Suzuki T. Matsumoto M. Oya Y. Katsumata 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,677(2):190-193
N1-Monoacetylspermine, N1,N12-diacetylspermine and N1-monoacetylspermidine were found to be good substrates for rat liver polyamine oxidase, but not for rat liver mitochondrial monoamine oxidase. N8-Monoacetylspermidine, monoacetylcadaverine, monoacetylputrescine and monoacetyl-1,3-diaminopropane were oxidized by the monoamine oxidase when the substrate concentration was 10.0 mM, but not by the polyamine oxidase. All the acetylpolyamines except N1,N12-diacetylspermine were also oxidized by hog kidney diamine oxidase although their affinities for the oxidase appeared low. The present data suggest that acetylpolyamines are not easily metabolized in vivo by either monoamine oxidase or diamine oxidase in mammalian tissues although N1-monoacetylspermine, N1,N12-diacetylspermine and N1-monoacetylspermidine are attacked by polyamine oxidase. 相似文献
19.
Usui F Shirasuna K Kimura H Tatsumi K Kawashima A Karasawa T Hida S Sagara J Taniguchi S Takahashi M 《Biochemical and biophysical research communications》2012,425(2):162-168
ObjectiveRecent investigations have suggested that the inflammasome plays a role in the development of vascular inflammation and atherosclerosis; however, its precise role remains controversial. We produced double-deficient mice for apolipoprotien E (Apoe) and caspase-1 (Casp1), a key component molecule of the inflammasome, and investigated the effect of caspase-1 deficiency on vascular inflammation and atherosclerosis.Methods and resultsAtherosclerotic plaque areas in whole aortas and aortic root of Western diet (WD)-fed Apoe?/?Casp1?/? mice were significantly reduced compared to those in Apoe?/? mice. The amount of macrophages and vascular smooth muscle cells in the plaques was also reduced in Apoe?/?Casp1?/? mice. No significant differences in plasma lipid profiles and body weight change were observed between these mice. Expression of interleukin (IL)-1β in the plaques as well as plasma levels of IL-1β, IL-1α, IL-6, CCL2, and TNF-α, in Apoe?/?Casp1?/? mice were lower than those in Apoe?/? mice. In vitro experiments showed that calcium phosphate crystals induced caspase-1 activation and secretion of IL-1β and IL-1α in macrophages.ConclusionOur findings suggest that caspase-1 plays a critical role in vascular inflammation and atherosclerosis, and that modulation of caspase-1 could be a potential target for prevention and treatment of atherosclerosis. 相似文献
20.
Katsuya Takenaka 《FEBS letters》2009,583(4):661-664
The chicken DT40 cell line is widely used for gene knock-outs. We attempted to introduce a polymerase-dead point mutation into Polκ, a polymerase for translesion DNA synthesis, taking advantage of the highly efficient targeted integration in DT40 cells. The resulting cells (REV3−/−POLK/pol-dead) proliferated with the same kinetics as the parental REV3−/− cells. Though the mock-treated REV3−/−POLK/mock cells showed the same sensitivity as the parental REV3−/− cells to methyl methanesulfonate, the REV3−/−POLK/pol-dead cells demonstrated the same sensitivity as the REV3−/−POLK/− double knock-out cells. This implies that the presence of the polymerase-dead Polκ does not interfere with other polymerases repairing monoalkylation damage. 相似文献