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941.
Savaskan NE Rocha L Kotter MR Baer A Lubec G van Meeteren LA Kishi Y Aoki J Moolenaar WH Nitsch R Bräuer AU 《Cellular and molecular life sciences : CMLS》2007,64(2):230-243
Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive
lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling,
demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in
the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly
found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal
cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes
adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain
and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries.
Received 18 September 2006; received after revision 30 October 2006; accepted 4 December 2006 相似文献
942.
Phosphatidylinositol 3-kinase (PI3-kinase) activity has been implicated in regulating cell cycle progression at distinct points
in the cell cycle by preventing cell cycle arrest or apoptosis. In this study, the role of PI3-kinase activity during the
entire G1 phase of the ongoing cell cycle was studied in Chinese hamster ovary (CHO) cells synchronized by mitotic shake-off.
We show that inhibition of PI3-kinase activity during and 2 h after mitosis inhibited cell cycle progression into S phase.
In the presence of the PI3-kinase inhibitor wortmannin or LY294002, cells were arrested during early G1 phase, leading to
the expression of the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PI3-kinase activity
is required for progression through the M/G1 phase. In the absence of PI3-kinase activity, cells are induced for apoptosis
in this particular phase of the cell cycle.
Received 7 September 2005; received after revision 26 October 2005; accepted 11 November 2005 相似文献
943.
Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract 总被引:1,自引:0,他引:1
Zara F Biancheri R Bruno C Bordo L Assereto S Gazzerro E Sotgia F Wang XB Gianotti S Stringara S Pedemonte M Uziel G Rossi A Schenone A Tortori-Donati P van der Knaap MS Lisanti MP Minetti C 《Nature genetics》2006,38(10):1111-1113
We describe a new autosomal recessive white matter disorder ('hypomyelination and congenital cataract') characterized by hypomyelination of the central and peripheral nervous system, progressive neurological impairment and congenital cataract. We identified mutations in five affected families, resulting in a deficiency of hyccin, a newly identified 521-amino acid membrane protein. Our study highlights the essential role of hyccin in central and peripheral myelination. 相似文献
944.
Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure
Tammo Müller Christin Dewitz Jessica Schmitz Anna Sophia Schröder Jan Hinrich Bräsen Brent R. Stockwell James M. Murphy Ulrich Kunzendorf Stefan Krautwald 《Cellular and molecular life sciences : CMLS》2017,74(19):3631-3645
Ferroptosis is a recently recognized caspase-independent form of regulated cell death that is characterized by the accumulation of lethal lipid ROS produced through iron-dependent lipid peroxidation. Considering that regulation of fatty acid metabolism is responsible for the membrane-resident pool of oxidizable fatty acids that undergo lipid peroxidation in ferroptotic processes, we examined the contribution of the key fatty acid metabolism enzyme, acyl-CoA synthetase long-chain family member 4 (ACSL4), in regulating ferroptosis. By using CRISPR/Cas9 technology, we found that knockout of Acsl4 in ferroptosis-sensitive murine and human cells conferred protection from erastin- and RSL3-induced cell death. In the same cell types, deletion of mixed lineage kinase domain-like (Mlkl) blocked susceptibility to necroptosis, as expected. Surprisingly, these studies also revealed ferroptosis and necroptosis are alternative, in that resistance to one pathway sensitized cells to death via the other pathway. These data suggest a mechanism by which one regulated necrosis pathway compensates for another when either ferroptosis or necroptosis is compromised. We verified the synergistic contributions of ferroptosis and necroptosis to tissue damage during acute organ failure in vivo. Interestingly, in the course of pathophysiological acute ischemic kidney injury, ACSL4 was initially upregulated and its expression level correlated with the severity of tissue damage. Together, our findings reveal ACSL4 to be a reliable biomarker of the emerging cell death modality of ferroptosis, which may also serve as a novel therapeutic target in preventing pathological cell death processes. 相似文献
945.
Verónica Parrillas Laura Martínez-Muñoz Borja L. Holgado Amit Kumar Graciela Cascio Pilar Lucas José Miguel Rodríguez-Frade Marcos Malumbres Ana C. Carrera Karel HM van Wely Mario Mellado 《Cellular and molecular life sciences : CMLS》2013,70(3):545-558
Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma. 相似文献
946.
Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response 总被引:1,自引:1,他引:0
947.
Geometry sensing by dendritic cells dictates spatial organization and PGE2-induced dissolution of podosomes 总被引:1,自引:1,他引:0
van den Dries K van Helden SF Riet Jt Diez-Ahedo R Manzo C Oud MM van Leeuwen FN Brock R Garcia-Parajo MF Cambi A Figdor CG 《Cellular and molecular life sciences : CMLS》2012,69(11):1889-1901
Assembly and disassembly of adhesion structures such as focal adhesions (FAs) and podosomes regulate cell adhesion and differentiation. On antigen-presenting dendritic cells (DCs), acquisition of a migratory and immunostimulatory phenotype depends on podosome dissolution by prostaglandin E(2) (PGE(2)). Whereas the effects of physico-chemical and topographical cues have been extensively studied on FAs, little is known about how podosomes respond to these signals. Here, we show that, unlike for FAs, podosome formation is not controlled by substrate physico-chemical properties. We demonstrate that cell adhesion is the only prerequisite for podosome formation and that substrate availability dictates podosome density. Interestingly, we show that DCs sense 3-dimensional (3-D) geometry by aligning podosomes along the edges of 3-D micropatterned surfaces. Finally, whereas on a 2-dimensional (2-D) surface PGE(2) causes a rapid increase in activated RhoA levels leading to fast podosome dissolution, 3-D geometric cues prevent PGE(2)-mediated RhoA activation resulting in impaired podosome dissolution even after prolonged stimulation. Our findings indicate that 2-D and 3-D geometric cues control the spatial organization of podosomes. More importantly, our studies demonstrate the importance of substrate dimensionality in regulating podosome dissolution and suggest that substrate dimensionality plays an important role in controlling DC activation, a key process in initiating immune responses. 相似文献
948.
Boros S Xi Q Dimke H van der Kemp AW Tudpor K Verkaart S Lee KP Bindels RJ Hoenderop JG 《Cellular and molecular life sciences : CMLS》2012,69(6):981-992
Tissue transglutaminase (tTG) is a multifunctional Ca2+-dependent enzyme, catalyzing protein crosslinking. The transient receptor potential vanilloid (TRPV) family of cation channels
was recently shown to contribute to the regulation of TG activities in keratinocytes and hence skin barrier formation. In
kidney, where active transcellular Ca2+ transport via TRPV5 predominates, the potential effect of tTG remains unknown. A multitude of factors regulate TRPV5, many
secreted into the pro-urine and acting from the extracellular side. We detected tTG in mouse urine and in the apical medium
of polarized cultures of rabbit connecting tubule and cortical collecting duct (CNT/CCD) cells. Extracellular application
of tTG significantly reduced TRPV5 activity in human embryonic kidney cells transiently expressing the channel. Similarly,
a strong inhibition of transepithelial Ca2+ transport was observed after apical application of purified tTG to polarized rabbit CNT/CCD cells. Furthermore, tTG promoted
the aggregation of the plasma membrane-associated fraction of TRPV5. Using patch clamp analysis, we observed a reduction in
the pore diameter after tTG treatment, suggesting distinct structural changes in TRPV5 upon crosslinking by tTG. As N-linked
glycosylation of TRPV5 is a key step in regulating channel function, we determined the effect of tTG in the N-glycosylation-deficient
TRPV5 mutant. In the absence of N-linked glycosylation, TRPV5 was insensitive to tTG. Taken together, these observations imply
that tTG is a novel extracellular enzyme inhibiting the activity of TRPV5. The inhibition of TRPV5 occurs in an N-glycosylation-dependent
manner, signifying a common final pathway by which distinct extracellular factors regulate channel activity. 相似文献
949.
Van Houdt JK Nowakowska BA Sousa SB van Schaik BD Seuntjens E Avonce N Sifrim A Abdul-Rahman OA van den Boogaard MJ Bottani A Castori M Cormier-Daire V Deardorff MA Filges I Fryer A Fryns JP Gana S Garavelli L Gillessen-Kaesbach G Hall BD Horn D Huylebroeck D Klapecki J Krajewska-Walasek M Kuechler A Lines MA Maas S Macdermot KD McKee S Magee A de Man SA Moreau Y Morice-Picard F Obersztyn E Pilch J Rosser E Shannon N Stolte-Dijkstra I Van Dijck P Vilain C Vogels A Wakeling E Wieczorek D 《Nature genetics》2012,44(4):445-9, S1
950.
Albers CA Paul DS Schulze H Freson K Stephens JC Smethurst PA Jolley JD Cvejic A Kostadima M Bertone P Breuning MH Debili N Deloukas P Favier R Fiedler J Hobbs CM Huang N Hurles ME Kiddle G Krapels I Nurden P Ruivenkamp CA Sambrook JG Smith K Stemple DL Strauss G Thys C van Geet C Newbury-Ecob R Ouwehand WH Ghevaert C 《Nature genetics》2012,44(4):435-9, S1-2