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1.
Alayna E. Loiselle Shane A. J. Lloyd Emmanuel M. Paul Gregory S. Lewis Henry J. Donahue 《PloS one》2013,8(11)
Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair. 相似文献
2.
Brigitte Aupetit Alexandre Ghazi Nicole Blanchouin Ren e Toury Emmanuel Shechter Jean-Claude Legrand 《BBA》1988,936(3):325-331
In this study we have measured, under experimental conditions which maintained efficient coupling, respiratory intensity, respiratory control, oxidative phosphorylation capacity and protonmotive force. Succinate cytochrome-c reductase and cytochrome-c oxidase activities were also studied. These investigations were carried out using kidney mitochondria from cyclosporine-treated rats (in vivo studies) and from untreated rats in the presence of cyclosporine (in vitro studies). Inhibition of respiratory intensity by cyclosporine did not exceed 21.1% in vitro and 15.9% in vivo. Since there was no in vitro inhibition of succinate cytochrome-c reductase and cytochrome-c oxidase activities, the slowing of electron flow observed can be interpreted as a consequence of an effect produced by cyclosporine between cytochromes b and c1. Cyclosporine had no effect on respiratory control either in vitro or in vivo. Statistically significant inhibition of the oxidative phosphorylation was observed both in vitro (6.6%) and in vivo (12.1%). Moreover, cyclosporine did not induce any change of membrane potential either in vivo or in vitro. Our findings show that cyclosporine is neither a protonophore, nor a potassium ionophore. In cyclosporine-treated rats we noticed a decrease of protein in subcellular fraction, including the mitochondrial fraction. The role of the inhibition respiratory characteristics by cyclosporine in nephrotoxicity in vivo must take account of these two parameters: inhibition of the respiratory characteristics measured in vitro and diminution of mitochondrial protein in cyclosporine-treated rats. 相似文献
3.
Role of RNA structures in c-myc and c-fos gene regulations 总被引:1,自引:0,他引:1
4.
J Gallego J C Fort M Lethielleux B Chambille G Vardon C Jacquemin 《Journal de physiologie》1985,80(5):349-354
Inspiratory duration (TI), cycle duration (TTOT), and tidal volume (VT) were continuously measured in 11 normal subjects during 400 respiratory cycles. Small breath to breath changes in these variables were separately analyzed. For each of these variables, successive observations are not statistically independent; "large" values tend to be followed by "large" values. A respiratory feedback may be involved in this sequential dependence. In that case, any known system of respiratory control could be associated with it, even those with time constant or delay longer than one cycle duration. 相似文献
5.
Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes. 总被引:13,自引:2,他引:11 下载免费PDF全文
We report the first and complete nucleotide sequence of a human gamma 3 heavy chain constant region gene (C gamma 3). This gene displays the same organization than the others C gamma genes and exhibits normal RNA splice and polyadenylation sites. A comparison of its primary sequence with those of C gamma 1, C gamma 2 and C gamma 4 genes confirms the high degree of homology (95%) of the human family in both coding and non-coding regions, and the divergence of the hinge region. The C gamma 3 gene we sequenced codes for a Gm(b) gamma 3 chain (EZZ). Comparison with other known protein sequences reveals that only two specific aminoacids are involved in the Gm(b) and Gm(g) allotypes, which suggests an important part of the spatial configuration in the allotypic specificities. 相似文献
6.
James M. Berger Paul J. Jackson Nigel J. Robinson Leah D. Lujan Emmanuel Delhaize 《Plant cell reports》1989,7(8):632-635
Suspension cultures of Datura innoxia cells were pulse-labeled with [35S]cysteine, then exposed to Cd to determine whether there is a direct precursor-product relationship amongst the different forms of the Cd-induced polypeptides, poly(-glutamylcysteinyl)glycines [(EC)nG, n=2 to 5]. Degradation of the polypeptides and possible regeneration of the [35S]-labeled glutathione and cysteine pools were also examined. After 2 h of exposure to [35S]cysteine, about 70% of the [35S]cysteine in the soluble fraction of the cell was incorporated into [35S]glutathione before exposure of the cells to Cd. One h after Cd exposure, most of the cellular [35S]glutathione was depleted and label was incorporated into (EC)nG. Analysis of [35S](EC)nG by reverse phase HPLC showed no direct precursor-product relationship between the synthesis of the shorter and longer chain forms. However, the rate of synthesis of the different polypeptides was linear for 32 h after Cd exposure. There was no evidence of degradation of [35S](EC)nG nor was it excreted into the medium within this period. From these results it is suggested that in the presence of Cd, a large pool of (EC)nG is unavailable for elongation to (EC)n+1G.Abbreviations (EC)nG
Poly(-glutamylcysteinyl)glycine
- HPLC
High pressure liquid chromatography
- CPM
Counts per minute 相似文献
7.
Emmanuel Sivvas Georgia Voukelatou Dionissios Papaioannou Alexios J. Aletras Elias D. Kouvelas 《Journal of neurochemistry》1994,63(4):1544-1550
Abstract: The synthesis of (2 S ,3 S ,4 S )-4-[1-(4-azidobenzamidomethyl)ethenyl]-2-carboxy-3-pyrrolidineacetic acid (ABCPA) is described. This novel kainic acid analogue, bearing a photolabile functionality on the isopropenyl side chain, was proven to be a good inhibitor of [3 H]CNQX and [3 H]kainic acid binding on chick cerebellar membranes. [3 H]ABCPA was photoaffinity cross-linked on the membrane fraction of chick cerebellum. Electrophoretic analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two major radioactive bands with apparent molecular masses of 45 and 33.5 kDa. [3 H]ABCPA incorporation in both bands was completely blocked by 2 m M CNQX. When photoaffinity labeling was performed in the presence of 2 m M kainic acid, incorporation of [3 H]ABCPA was blocked by ∼70% in the 45-kDa band and by 18% in the 33.5-kDa band. Incorporation of radioactivity in both bands was blocked by ∼30% with 10 m M glutamate. 相似文献
8.
Emmanuel Katsanis Maria A. Bausero Hong Xu Paul J. Orchard Zhiyi Xu R. Scott Melvor Adrienne A. Brian Bruce R. Blazar 《Cancer immunology, immunotherapy : CII》1994,38(2):135-141
We determined the expression of intercellular adhesion molecules (ICAM) on neuro-2a cells in order to evaluate whether they were involved in cytolysis of murine neuroblastoma. Fluorescence-activated cell sorting analysis revealed that the control neomycin-resistance-genetransduced line (neuro-2a/LN) had poor expression of ICAM-1 (mean channel fluorescence, MCF=3.7). An ICAM-1-positive transfectant of neuro-2a (neuro-2a/ICAM-1+) (CMF=64.3) was generated to evaluate directly the role of this adhesion molecule in cytolysis. Neuro-2a/ICAM-1+ was more sensitive to LAK killing (69.7% at an effector-to-target ratio of 1001) compared to neuro-2a/LN (48.6%) (P<0.001). Blocking of neuro-2a/LN and neuro-2a/ICAM-1+ lysis with anti-ICAM-1 monoclonal antibodies (mAbs) did not account for all the LFA-1-dependent killing. These data indicate that even in neuro-2a/ICAM-1+ cells, other LFA-1 ligands participated in the effector-target interaction. Therefore, we examined these cell lines for ICAM-2 expression. Both neuro-2a/LN and neuro-2a/ICAM-1+ lines expressed ICAM-2 (MCF=16.4 and 16.5). ICAM-2 accounted for the majority of the LFA-1-dependent killing in the ICAM-1-negative target, neuro-2a/LN, while ICAM-1 played a primary role in the cytolysis of the ICAM-1+ transfectant. Inhibition of lysis in the presence of anti-ICAM-1 and ICAM-2 mAbs was comparable to that seen with the addition of anti-LFA-1 mAb, indicating that other LFA-1 ligands were not involved in this system. ICAM-1 expression was associated with decreased in vivo tumorigenicity; mice inoculated with neuro-2a/ICAM-1+ cells had a significantly longer survival compared to those receiving neuro-2a/LN cells (median survival time 35.5 versus 24.5 days) (P<0.001). It is important to note that ICAM-1 transfection of murine neuroblastoma did not alter its metastatic potential. We conclude that transfection of mouse neuroblastome with ICAM-1 increases its sensitivity to in vitro lysis and reduces its in vivo tumorgenicity. In ICAM-1-negative murine neuroblastoma cells, ICAM-2 plays a primary role in cell-mediated lysis.This work was supported in part by the Children's Cancer Research Fund, the Minnesota Medical Foundation, the Viking Children's Fund and NIH grants PO1-CA-21737, NO1-AI-85002. E. K. is a recipient of the Irvine McQuarrie Research Scholar Award and B. R. B. a recipient of the Edward Mallinkrodt Foundation Scholar Award 相似文献
9.
An understanding of plant responses to fluctuations in environment is critical to predictions of plant and ecosystem responses
to climate change. In the northern hemisphere, the northern limits of distribution of major biomes are probably determined
by the tolerance of their dominant physiognomic types (e.g., deciduous hardwood trees) to minimum winter temperatures and
can thus be predicted from long-term patterns of temperature fluctuations. At a more detailed level, the responses of functional
groups of plants to altered climate can be predicted from their known responses to fluctuations in soil resources (nutrients
and water) and the expected effect of climatic change on these soil resources. Laboratory and field experiments demonstrate
the feasibility of this approach. 相似文献
10.
Amira Azizan Stefano Anile Clayton K. Nielsen Emmanuel Paradis Sébastien Devillard 《Global Ecology and Biogeography》2023,32(10):1858-1869