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71.
Joanne M. Munck Alison M. Motley James M. Nuttall Ewald H. Hettema 《The Journal of cell biology》2009,187(4):463-471
Saccharomyces cerevisiae Pex3p has been shown to act at the ER during de novo peroxisome formation. However, its steady state is at the peroxisomal membrane, where its role is debated. Here we show that Pex3p has a dual function: one in peroxisome formation and one in peroxisome segregation. We show that the peroxisome retention factor Inp1p interacts physically with Pex3p in vitro and in vivo, and split-GFP analysis shows that the site of interaction is the peroxisomal membrane. Furthermore, we have generated PEX3 alleles that support peroxisome formation but fail to support recruitment of Inp1p to peroxisomes, and as a consequence are affected in peroxisome segregation. We conclude that Pex3p functions as an anchor for Inp1p at the peroxisomal membrane, and that this function is independent of its role at the ER in peroxisome biogenesis. 相似文献
72.
Kratzer A Buchebner M Pfeifer T Becker TM Uray G Miyazaki M Miyazaki-Anzai S Ebner B Chandak PG Kadam RS Calayir E Rathke N Ahammer H Radovic B Trauner M Hoefler G Kompella UB Fauler G Levi M Levak-Frank S Kostner GM Kratky D 《Journal of lipid research》2009,50(2):312-326
Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism. LXR agonists have been shown to limit the cellular cholesterol content by inducing reverse cholesterol transport, increasing bile acid production, and inhibiting intestinal cholesterol absorption. Most of them, however, also increase lipogenesis via sterol regulatory element-binding protein-1c (SREBP1c) and carbohydrate response element-binding protein activation resulting in hypertriglyceridemia and liver steatosis. We report on the antiatherogenic properties of the steroidal liver X receptor agonist N,N-dimethyl-3beta-hydroxy-cholenamide (DMHCA) in apolipoprotein E (apoE)-deficient mice. Long-term administration of DMHCA (11 weeks) significantly reduced lesion formation in male and female apoE-null mice. Notably, DMHCA neither increased hepatic triglyceride (TG) levels in male nor female apoE-deficient mice. ATP binding cassette transporter A1 and G1 and cholesterol 7alpha-hydroxylase mRNA abundances were increased, whereas SREBP1c mRNA expression was unchanged in liver, and even decreased in macrophages and intestine. Short-term treatment revealed even higher changes on mRNA regulation. Our data provide evidence that DMHCA is a strong candidate as therapeutic agent for the treatment or prevention of atherosclerosis, circumventing the negative side effects of other LXR agonists. 相似文献
73.
Cell death in rheumatoid arthritis 总被引:2,自引:0,他引:2
74.
De Ketelaere A Vermeulen L Vialard J Van De Weyer I Van Wauwe J Haegeman G Moelans I 《FEBS letters》2004,566(1-3):60-64
Glycogen synthase kinase-3beta (GSK-3beta) is a key component of several signaling pathways. We found that a short variant of 'TNF-like weak inducer of apoptosis' (shortTWEAK) formed a complex with GSK-3beta in a yeast two-hybrid system. We demonstrate that shortTWEAK and GSK-3beta colocalize in the nucleus of human neuroblastoma cells. We also show that TWEAK is internalized in different cell lines and that it translocates to the nucleus. This event causes the degradation of IkappaBalpha, the nuclear translocation of both GSK-3beta and p65, and the induction of NF-kappaB-driven gene expression. We demonstrate that the induction of IL-8 expression by TWEAK can be counteracted by LiCl. Taken together, these data suggest that GSK-3beta plays an important role in the signal transduction pathway between TWEAK and NF-kappaB. 相似文献
75.
Holm PC Rodríguez FJ Kresse A Canals JM Silos-Santiago I Arenas E 《Development (Cambridge, England)》2003,130(15):3535-3545
The role of glial cell-line derived neurotrophic factor (GDNF) and neurotrophins in the development of locus coeruleus noradrenergic neurons was evaluated. We found that two neurotrophic factors previously reported to prevent the degeneration of lesioned adult central noradrenergic neurons, GDNF and neurotrophin 3 (NT3), do not play significant roles in the prenatal development of locus coeruleus noradrenergic neurons, as demonstrated by: (1) the lack of alterations in double Gdnf/Nt3 null mutant mice; and (2) the lack of survival-promoting effects of GDNF and/or NT3 in rat E13.5 primary cultures. In contrast, null mutant mice for TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor and neurotrophin 4, displayed a clear loss of locus coeruleus noradrenergic neurons. In accordance with this, treatment of rat E13.5 primary cultures with TrkB ligands prevented the early loss of noradrenergic neurons and maintained their survival for up to 6 days in vitro. Moreover, an additional 5-10-fold increase in the number of tyrosine hydroxylase positive noradrenergic neurons was detected after 12 hours in culture. This second effect of TrkB ligands involved neither proliferation nor survival, because the number of BrdU- or TUNEL-positive noradrenergic neurons did not change and the effect was elicited by delayed administration of either factor. Because TrkB ligands increased the number of tyrosine hydroxylase-positive cells expressing Phox2a, a paired homeodomain protein required for the development of locus coeruleus noradrenergic neurons, but did not affect the number of Phox2a-positive tyrosine hydroxylase-negative cells, our results suggest that the second effect of TrkB ligands may involve promoting or inducing a noradrenergic phenotype. In summary, our findings suggest that, unlike NT3 and GDNF, TrkB ligands are required and sufficient to promote the development of central noradrenergic neurons. 相似文献
76.
Cutting edge: the minor histocompatibility antigen H60 peptide interacts with both H-2Kb and NKG2D 总被引:2,自引:0,他引:2
Cerwenka A O'Callaghan CA Hamerman JA Yadav R Ajayi W Roopenian DC Joyce S Lanier LL 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(7):3131-3134
Minor histocompatibility Ags elicit cell-mediated immune responses and graft rejection in individuals receiving MHC-matched tissues. H60 represents a dominant Ag that elicits a strong CTL response in C57BL/6 mice immunized against BALB.B. An 8-aa peptide in the H60 protein is presented by H-2K(b) and this is recognized by the TCR as an alloantigen. The intact H60 glycoprotein is a ligand for the costimulatory NKG2D receptor that is expressed by activated CD8(+) T cells. Thus, H60 may provide both an allogeneic peptide and its own costimulation. We show that mutation of an H-2K(b)-binding anchor residue in the H60 peptide completely abrogates binding of H60 glycoprotein to NKG2D and a synthetic H60 peptide partially blocks the binding of NKG2D to its ligand. Ligands of the human NKG2D receptor are remarkably polymorphic, suggesting that these may also serve as minor histocompatibility Ags. 相似文献
77.
Jack E. Bodwell Li-Ming Hu Jiong-Ming Hu Eduardo Ortí Allan Munck 《The Journal of steroid biochemistry and molecular biology》1993,47(1-6):31-38
The dependence of hormone binding to glucocorticoid receptors (GRs) on cellular ATP levels led us to propose that GRs normally traverse an ATP-dependent cycle, possibly involving receptor phosphorylation, and that without ATP they accumulate in a form that cannot bind hormone. We identified such a form, the null receptor, in ATP-depleted cells. GRs are basally phosphorylated, and become hyperphosphorylated after treatment with hormone (but not RU486). In mouse receptors we have identified 7 phosphorylated sites, all in the N-terminal domain. Most are on serines and lie within a transactivation region. The time-course of hormone-induced hyperphosphorylation indicates that the primary substrates for hyperphosphorylation are the activated receptors; unliganded and hormone-liganded nonactivated receptors become hyperphosphorylated more slowly. After dissociation of hormone, most receptors appear to be recycled and reutilized in hyperphosphorylated form. From these and related observations, we have concluded that the postulated ATP-dependent cycle can be accounted for by hormone-induced or spontaneous dissociation of receptor-Hsp90 complexes, followed by reassociation of unliganded receptors with Hsp90 via an ATP-dependent reaction like that demonstrated in cell-free systems. Other steroid hormone receptors might traverse a similar cycle. Four of the 7 phosphorylated sites in the N-terminal domain are in consensus sequences for p34cdc2 kinases important in cell cycle regulation. This observation, along with the known cell cycle-dependence of sensitivity to glucocorticoids and other evidence, point to a role for receptor phosphorylation in controlling responses to glucocorticoids through the cell cycle. 相似文献
78.
Summary A method for the production of somatic embryos and subsequent plant regeneration for Anthurium andraeanum Linden ex André (Monocotyledonae) hybrids is described. Whole leaf blade explants, derived from plantlets grown in vitro, formed translucent embryogénic calli at their basal ends within one month of culture in the dark. Secondary somatic embryos formed frequently and without an intervening callus on surfaces of primary embryos. Embryogenesis was induced with three genotypes using a modified half-strength Murashige and Skoog (MS) medium supplemented with 1.0 to 4.0 mg l–1 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.33 to 1.0 mg l–1 kinetin. A combination of 2% sucrose with 1% glucose in the medium favored embryogenesis over 3% sucrose alone. Whole leaf blades on medium solidified with 0.18% Gelrite produced more somatic embryos than leaves on medium with 0.7% Bacto-agar. Within two to three months after culture initiation, embryos were transferred to modified MS medium containing 0.2 mg l–1 6-benzyladenine (BA) and 2% sucrose and placed in the light for conversion into plantlets. Rooted plantlets were recovered and transferred into pots with tree fern fiber medium and grown in the greenhouse.Abbreviations MS
Murashige and Skoog (1962)
- 2,4-D
2,4 dichlorophenoxyacetic acid
- BA
6-benzyladenine 相似文献
79.
We present a review of galanin in the brain from a historical perspective of the development of "chemoarchitectonics" and "brain cartography" accomplished in the Histopharmacology Section at the National Institutes of Health. It was the mapping of potential brain neuroregulators that served as a springboard of ideas from which behavioral studies emanate. The integration of the known localization of neurotransmitter/neuromodulatory nerves ("chemoarchitectonic maps") and receptor binding sites with biochemical data derived from brain micropunches coupled with behavioral analysis at the level of discrete brain allows one to define the anatomical circuits which support behavioral changes and which ultimately will improve our understanding of mental disorders. 相似文献
80.
Neumann A Engelmann T Schmitz R Greiser Y Orthaus A Diekert G 《Archives of microbiology》2004,181(3):245-249
Desulfitobacterium hafniense and Desulfitobacterium sp. strain PCE-S grew under anoxic conditions with a variety of phenyl methyl ethers as electron donors in combination with fumarate as electron acceptor. The phenyl methyl ethers were O-demethylated to the corresponding phenol compounds. O-demethylation was strictly dependent on the presence of fumarate; no O-demethylation occurred with CO2 as electron acceptor. One mol phenyl methyl ether R-O-CH3 was O-demethylated to R-OH per 3 mol fumarate reduced to succinate. The growth yields with vanillate or syringate plus fumarate were approximately 15 g cells (dry weight) per mol methyl moiety converted. D. hafniense utilized vanillate or syringate as an electron donor for reductive dehalogenation of 3-Cl-4-hydroxyphenylacetate, whereas strain PCE-S was not able to dechlorinate tetrachloroethene with phenyl methyl ethers. Crude extracts of both organisms showed O-demethylase activity in the O-demethylase assay with vanillate or syringate as substrates when the organism was grown on syringate plus fumarate. Besides the homoacetogenic bacteria, only growing cells of Desulfitobacterium frappieri PCP-1 have thus far been reported to be capable of phenyl methyl ether O-demethylation. This present study is the first report of Desulfitobacteria utilizing phenyl methyl ethers as electron donors for fumarate reduction and for growth.Abbreviations PCE Tetrachloroethene - TCE Trichloroethene - DCE cis-1,2-Dichloroethene - ClOHPA 3-Cl-4-Hydroxyphenylacetate - OHPA 4-Hydroxyphenylacetate - FH4 Tetrahydrofolate 相似文献