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941.
Signaling by tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) is essential for the differentiation
of monocytes/macrophages into osteoclasts. We show here that TRANCE selectively activates Rac1, but not Rac2 in osteoclast
precursors. Expression of a dominant interfering mutant of TNF receptor-associated factor (TRAF)6 blocks TRANCE-mediated Rac1
activation, indicating that Rac1 lies downstream of TRAF6. Osteoclast precursors expressing a dominant negative Rac1N17 are
defective in TRANCE-induced IKK activation and IκBα degradation resulting in inhibition of NFκB-dependent reporter gene activity.
In addition, Rac1 acts upstream of TAK1 to induce NF-κB activation and is required for the normal differentiation of osteoclast
precursors. Thus, Rac1 may represent a key regulator for differentiation of osteoclasts through the activation of NF-κB. 相似文献
942.
BACKGROUND AND AIMS: Determining the mode of action of allelochemicals is one of the challenging aspects in allelopathic studies. Recently, allelochemicals have been proposed to cause oxidative stress in target tissue and induce an antioxidant mechanism. alpha-Pinene, one of the common monoterpenoids emitted from several aromatic plants including forest trees, is known for its growth-inhibitory activity. However, its mechanism of action remains unexplored. The aim of the present study was to determine the inhibitory effect of alpha-pinene on root growth and generation of reactive oxygen species, as indicators of oxidative stress and changes in activities of antioxidant enzymes. METHODS: Effects of alpha-pinene on early root growth were studied in five test species, Cassia occidentalis, Amaranthus viridis, Triticum aestivum, Pisum sativum and Cicer arietinum. Electrolyte leakage, lipid peroxidation, hydrogen peroxide generation, proline accumulation, and activities of the enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and glutathione reductase (GR) were studied in roots of C. occidentalis. KEY RESULTS: alpha-Pinene inhibited the radicle growth of all the test species. Exposure of C. occidentalis roots to alpha-pinene enhanced solute leakage, and increased levels of malondialdehyde, proline and hydrogen peroxide, indicating lipid peroxidation and induction of oxidative stress. Activities of the antioxidant enzymes SOD, CAT, GPX, APX and GR were significantly elevated, thereby indicating the enhanced generation of reactive oxygen species (ROS) upon alpha-pinene exposure. Increased levels of scavenging enzymes indicates their induction as a secondary defence mechanism in response to alpha-pinene. CONCLUSIONS: It is concluded that alpha-pinene inhibits early root growth and causes oxidative damage in root tissue through enhanced generation of ROS, as indicated by increased lipid peroxidation, disruption of membrane integrity and elevated antioxidant enzyme levels. 相似文献
943.
In this study, an attempt has been made to develop a method for predicting weak hydrogen bonding interactions, namely, C alpha-H...O and C alpha-H...pi interactions in proteins using artificial neural network. Both standard feed-forward neural network (FNN) and recurrent neural networks (RNN) have been trained and tested using five-fold cross-validation on a non-homologous dataset of 2298 protein chains where no pair of sequences has more than 25% sequence identity. It has been found that the prediction accuracy varies with the separation distance between donor and acceptor residues. The maximum sensitivity achieved with RNN for C alpha-H...O is 51.2% when donor and acceptor residues are four residues apart (i.e. at delta D-A = 4) and for C alpha-H...pi is 82.1% at delta D-A = 3. The performance of RNN is increased by 1-3% for both types of interactions when PSIPRED predicted protein secondary structure is used. Overall, RNN performs better than feed-forward networks at all separation distances between donor-acceptor pair for both types of interactions. Based on the observations, a web server CHpredict (available at http://www.imtech.res.in/raghava/chpredict/) has been developed for predicting donor and acceptor residues in C alpha-H...O and C alpha-H...pi interactions in proteins. 相似文献
944.
Sobti RC Onsory K Al-Badran AI Kaur P Watanabe M Krishan A Mohan H 《DNA and cell biology》2006,25(5):287-294
To investigate the involvement of the CYP17, SRD5A2, CYP1B1, and CYP2D6 variants with prostate cancer, a case-control study of 100 patients and an equal number of age-matched control men was conducted. There appears to be a nonsignificant increase with risk of prostate cancer for individuals carrying one copy of the CYP17 A2 allele (OR, 1.80; 95% CI, 0.99-3.29, P=0.05). The risk was increased in individuals having two A2 alleles (OR; 2.81, 95% CI, 1.06-7.40, P=0.03). Compared with men having the VV genotype of SRD5A2 gene, there was no significant association between the VL genotype and the risk of prostate cancer (OR; 0.54, 95% CI; 0.29-1.03, P=0.06). There was no difference in the occurrence of the genotype LL between controls and prostate cancer patients (OR; 0.90, 95% CI; 0.43-1.89, P=0.79). There was a nonsignificant increased risk of prostate cancer for individuals carrying the CYP1B1Leu/Val genotype (OR, 1.70, 95% CI, 0.91-3.17, P =0.09), which was increased in those having the Val/Val allele (OR, 3.38; 95% CI, 1.13-10.07, P=0.02). Relative to men homozygous for the wild-type allele in CYP2D6 gene, those heterozygous for the B allele had an odds ratio of 1.78 (95% CI, 0.76-4.17, P=0.18) for patients, and for homozygous individuals, it was 1.95 (0.55-6.93, P=0.30). These observations have suggested that the CYP17 A2/A2, CYP1B1 Val/Val, and CYP2D6 genotypes may be associated with an altered risk of prostate cancer, while the CYP2D6 and SRD5A2 V89L polymorphism have no association with its risk in the North Indian population. 相似文献
945.
Sobti RC Kaur P Kaur S Janmeja AK Jindal SK Kishan J Raimondi S 《DNA and cell biology》2006,25(8):484-489
DNA ligases play an essential role in repair, replication, and recombination of DNA, and catalyzes the formation of a phosphodiester bond at a nick junction on single- and double-strand breaks. We have conducted a hospital-based case-control study to examine the role of polymorphism of DNA repair gene ligase I (LIGI) in the context of lung cancer risk for north Indian population. One hundred, fifty-one primary lung cancer cases and an equal number of matching hospital controls were collected. The LIGI polymorphism was determined by using the PCR-RFLP method. The association between polymorphisms in the LIGI gene with the risk of lung cancer was estimated by computing odds ratios (ORs) and a 95% confidence interval (CI) using a Multivariate Logistic Regression Analysis. The risk for lung cancer was not associated for individuals featuring LIGI (AC) (OR -0.8, 95% CI = 0.44-1.40) and (AA) (OR -0.8, 95% CI = 0.41-1.80) genotypes. The DNA repair gene (LIGI) may not be playing an important role in modulating the risk of lung cancer in the north Indian population. 相似文献
946.
A lectin from the seeds of Amaranthus viridis Linn has been purified by affinity chromatography on asialofetuin-linked amino activated silica. Amaranthus viridis lectin (AVL) has a native molecular mass of 67 kDa. It is a homodimer composed of two 36.6 kDa subunits. The lectin gave a single band in non-denaturing PAGE at pH 4.5 and pH 8.3 and a single peak on HPLC size exclusion and cation exchange columns. The purified lectin was specific for both T-antigen and N-acetyl-D-lactosamine, markers for various carcinomas, in addition to N-acetyl-D-galactosamine, asialofetuin and fetuin. This lectin reacted strongly with red blood cells (RBCs) from human ABO blood groups and rat. It also reacted with rabbit, sheep, goat and guinea pig RBCs. The lectin is a glycoprotein having no metal ion requirement for its activity. Denaturing agents such as urea, thiourea and guanidine-HCl had no effect on its activity when treated for 15 minutes. AVL showed significant antiproliferative activity towards HB98 and P388D1 murine cancer cell lines. It also exerted antifungal activity against phytopathogenic fungi Botrytis cincerea and Fusarium oxysporum but not against Rhizoctonia solani, Trichoderma reesei, Alternaria solani and Fusarium graminearum. 相似文献
947.
Human lung mast cells adhere to human airway smooth muscle, in part, via tumor suppressor in lung cancer-1 总被引:5,自引:0,他引:5
Yang W Kaur D Okayama Y Ito A Wardlaw AJ Brightling CE Bradding P 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(2):1238-1243
Mast cells infiltrate the airway smooth muscle (ASM) of patients with asthma, an event which is likely to be a key factor in the development of this disease. Adhesion is a fundamental mechanism facilitating cellular cross-talk. We have examined whether human lung mast cells (HLMC) and ASM adhere, and have also examined the mechanism involved. Primary cultures of HLMC and confluent human ASM were cocultured for 30 min, then nonadherent HLMC were removed by centrifugation. HLMC adhered avidly to ASM monolayers (mean +/- SEM adhesion 43.2 +/- 1.2%, n = 41). Adhesion was increased to 58.8 +/- 2.7% by 1 mM Mn2+ (p = 0.015), and was reduced by EDTA and EGTA to 20.5 +/- 1.5% and 21.0 +/- 1.3%, respectively (p < 0.0001). Adhesion-blocking Abs for ICAM-1, VCAM-1, CD18, and the alpha4 and beta1 integrins had no effect on HLMC adhesion. HLMC expressed tumor suppressor in lung cancer-1 (TSLC-1) and blocking this reduced adhesion from 38.5 +/- 4.8% to 28.3 +/- 3.7% (p = 0.004, n = 7). ASM did not express TSLC-1, indicating that TSLC-1 acts as a heterophilic adhesion molecule. In summary, HLMC adhere avidly to ASM in part via TSLC-1 and in part via an as-yet-undefined Ca2+-dependent pathway. This supports the hypothesis that adhesion is important in the recruitment and retention of HLMC by the ASM in asthma, and for the functional interaction of these cells. 相似文献
948.
Ishfaq Ahmed Sheikh Amit Kumar Singh Nagendra Singh Mau Sinha S. Baskar Singh Asha Bhushan Punit Kaur Alagiri Srinivasan Sujata Sharma Tej P. Singh 《The Journal of biological chemistry》2009,284(22):14849-14856
The crystal structure of the complex of lactoperoxidase (LPO) with its
physiological substrate thiocyanate (SCN–) has been
determined at 2.4Å resolution. It revealed that the
SCN– ion is bound to LPO in the distal heme cavity. The
observed orientation of the SCN– ion shows that the sulfur
atom is closer to the heme iron than the nitrogen atom. The nitrogen atom of
SCN– forms a hydrogen bond with a water (Wat) molecule at
position 6′. This water molecule is stabilized by two hydrogen bonds
with Gln423 Nε2 and Phe422 oxygen. In
contrast, the placement of the SCN– ion in the structure of
myeloperoxidase (MPO) occurs with an opposite orientation, in which the
nitrogen atom is closer to the heme iron than the sulfur atom. The site
corresponding to the positions of Gln423, Phe422 oxygen,
and Wat6′ in LPO is occupied primarily by the side chain of
Phe407 in MPO due to an entirely different conformation of the loop
corresponding to the segment Arg418–Phe431 of LPO.
This arrangement in MPO does not favor a similar orientation of the
SCN– ion. The orientation of the catalytic product
OSCN– as reported in the structure of
LPO·OSCN– is similar to the orientation of
SCN– in the structure of LPO·SCN–.
Similarly, in the structure of
LPO·SCN–·CN–, in which
CN– binds at Wat1, the position and orientation of
the SCN– ion are also identical to that observed in the
structure of LPO·SCN.Lactoperoxidase
(LPO4; EC 1.11.1.7) is
a Fe3+ heme enzyme that belongs to the mammalian peroxidase family
(1). The family of mammalian
peroxidases comprises lactoperoxidase
(2), eosinophil peroxidase
(3), thyroid peroxidase
(4), and myeloperoxidase (MPO)
(5). LPO, eosinophil
peroxidase, and MPO are responsible for antimicrobial function and innate
immune responses
(6–8),
whereas thyroid peroxidase plays a key role in thyroid hormone biosynthesis
(9). These peroxidases are
different from plant and fungal peroxidases because unlike plant and fungal
enzymes, the prosthetic heme group in mammalian peroxidases is covalently
linked to the protein (10).
There are also several striking structural and functional differences among
the mammalian peroxidases
(11). The heme group in MPO is
attached to the protein via three covalent linkages
(12), whereas LPO
(12,
13), eosinophil peroxidase
(12), and thyroid peroxidase
(12) contain only two ester
linkages. These covalent and various non-covalent linkages contribute
differentially to the high stability of the heme core as well as for the
peculiar values of their redox potentials
(2,
14). Furthermore, MPO consists
of two disulfide-linked protein chains, whereas LPO, eosinophil peroxidase,
and thyroid peroxidase are single chain proteins, although their chain lengths
differ greatly. In addition, their sequences contain several critical amino
acid differences that may also contribute to the variations in the
stereochemical environments of the substrate-binding sites. As a consequence
of these differences, the mammalian enzymes oxidize various inorganic ions
such as SCN–, Br–, Cl–, and
I– with differing specificities and potencies. Biochemical
studies have shown that LPO catalyzes preferentially the conversion of
SCN– to OSCN–
(15,
16), whereas MPO uses halides
(17,
18) with a preference for
chloride ion as the substrate. The preferences of eosinophil peroxidase and
thyroid peroxidase are bromide and iodide, respectively. However, the
stereochemical basis of the reported preferences for the substrates by
mammalian heme peroxidases is still unclear. So far, the structures of only
two mammalian enzymes, MPO and LPO, have been determined
(12,
13). It is of considerable
importance to identify the structural parameters that are responsible for the
subtle specificities. In the present work, we have attempted to address this
question through the new crystal structures of LPO complexes with
SCN– ions using goat, bovine, and buffalo lactoperoxidases.
Because the overall structures of complexes of SCN– with LPO
from all three species were found to be identical, the structure of the
complex of buffalo LPO with SCN– and the ternary complex with
SCN– and CN– will be discussed here, and
buffalo LPO will be termed hereafter as LPO. To highlight the factors
pertaining to binding specificity of SCN–, a comparison of
the structures of LPO·SCN– and
MPO·SCN– has also been made, revealing many valuable
differences pertaining to the observed orientations of the common substrate,
SCN– ion, when bound at the substrate-binding site in the
distal heme cavity of the two structures. The structures of
LPO·SCN– and MPO·SCN– clearly
show that the bound SCN– ions are present in the distal heme
cavity of two enzymes with opposite orientations. In the structure of
LPO·SCN–, the sulfur atom is closer to the heme iron
than the nitrogen atom, whereas in that of MPO·SCN–,
the nitrogen atom is closer to the heme iron than the sulfur atom. As a result
of this, the interactions of the SCN– ion in the distal site
of two proteins differ drastically. Gln423, a conserved water (Wat)
molecule at position 6′, and a well aligned carbonyl oxygen of
Phe422 in the proximity of the substrate-binding site in LPO
against a protruding Phe407 in MPO seem to play the key roles in
inducing the observed orientations of SCN– ions in LPO and
MPO. The structure of LPO·SCN– has also been compared
with the structure of its ternary complex with SCN– and
CN– ions. 相似文献
949.
950.
Vallo P Petrželková KJ Profousová I Petrášová J Pomajbíková K Leendertz F Hashimoto C Simmons N Babweteera F Machanda Z Piel A Robbins MM Boesch C Sanz C Morgan D Sommer V Furuichi T Fujita S Matsuzawa T Kaur T Huffman MA Modrý D 《American journal of physical anthropology》2012,148(4):525-533
The entodiniomorphid ciliate Troglodytella abrassarti is a colonic mutualist of great apes. Its host specificity makes it a suitable model for studies of primate evolution. We explored molecular diversity of T. abrassarti with regard to large geographical distribution and taxonomic diversity of its most common host, the chimpanzee. We found a very low diversification of T. abrassarti in chimpanzees across Africa. Distribution of two types of T. abrassarti supports evolutionary separation of the Western chimpanzee, P. t. verus, from populations in Central and East Africa. Type I T. abrassarti is probably a derived form, which corresponds with the Central African origin of chimpanzees and a founder event leading to P. t. verus. Exclusivity of the respective types of T. abrassarti to Western and Central/Eastern chimpanzees corroborates the difference found between an introduced population of presumed Western chimpanzees on Rubondo Island and an autochthonous population in mainland Tanzania. The identity of T. abrassarti from Nigerian P. t. ellioti and Central African chimpanzees suggests their close evolutionary relationship. Although this contrasts with published mtDNA data, it corroborates current opinion on the exclusive position of P. t. verus within the chimpanzee phylogeny. The type of T. abrassarti occurring in Central and East African common chimpanzee was confirmed also in bonobos. This may point to the presence of an ancestral Type II found throughout the Lower Guinean rainforest dating back to the common Pan ancestor. Alternatively, the molecular uniformity of T. abrassarti may imply a historical overlap of the species' distribution ranges. 相似文献