共查询到20条相似文献,搜索用时 15 毫秒
1.
Rafael Andrés Posada-Duque Omar Ramirez Steffen Härtel Nibaldo C. Inestrosa Felipe Bodaleo Christian González-Billault Alfredo Kirkwood Gloria Patricia Cardona-Gómez 《Cellular and molecular life sciences : CMLS》2017,74(1):153-172
CDK5 is a serine/threonine kinase that is involved in the normal function of the adult brain and plays a role in neurotransmission and synaptic plasticity. However, its over-regulation has been associated with Tau hyperphosphorylation and cognitive deficits. Our previous studies have demonstrated that CDK5 targeting using shRNA-miR provides neuroprotection and prevents cognitive deficits. Dendritic spine morphogenesis and forms of long-term synaptic plasticity—such as long-term potentiation (LTP)—have been proposed as essential processes of neuroplasticity. However, whether CDK5 participates in these processes remains controversial and depends on the experimental model. Using wild-type mice that received injections of CDK5 shRNA-miR in CA1 showed an increased LTP and recovered the PPF in deficient LTP of APPswe/PS1Δ9 transgenic mice. On mature hippocampal neurons CDK5, shRNA-miR for 12 days induced increased dendritic protrusion morphogenesis, which was dependent on Rac activity. In addition, silencing of CDK5 increased BDNF expression, temporarily increased phosphorylation of CaMKII, ERK, and CREB; and facilitated calcium signaling in neurites. Together, our data suggest that CDK5 downregulation induces synaptic plasticity in mature neurons involving Ca2+ signaling and BDNF/CREB activation. 相似文献
2.
Catherine Aude-Garcia Christian Villiers Serge M. Candéias Catherine Garrel Caroline Bertrand Véronique Collin Patrice N. Marche Evelyne Jouvin-Marche 《Cellular and molecular life sciences : CMLS》2011,68(4):687-696
The cellular prion glycoprotein (PrPC) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate
in vitro and in vivo that PrPC is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione,
we show that PrP−/− thymocytes display a higher susceptibility to H2O2 exposure than PrP+/+ cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level
of ROS, PrP−/− thymocytes are more sensitive to oxidative stress. PrPC function appears to be specific for oxidative stress, since no significant differences are observed between PrP−/− and PrP+/+ mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation
in the thymus. Taken together, our results clearly ascribe to PrPC a protective function in thymocytes against oxidative stress. 相似文献
3.
Pál B Pór A Szucs G Kovács I Rusznák Z 《Cellular and molecular life sciences : CMLS》2003,60(10):2189-2199
A hyperpolarization-activated current recorded from the pyramidal cells of the dorsal cochlear nucleus was investigated in the present study by using 150- to 200-m-thick brain slices prepared from 6- to 14-day-old Wistar rats. The pyramidal neurones exhibited a slowly activating inward current on hyperpolarization. The reversal potential of this component was –32 ± 3 mV (mean ± SE, n = 6), while its half-activation voltage was –99 ± 1 mV with a slope factor of 10.9 ± 0.4 mV (n = 27). This current was highly sensitive to the extracellular application of both 1 mM Cs+ and 10 M ZD7288. The electrophysiological properties and the pharmacological sensitivity of this current indicated that it corresponded to a hyperpolarization-activated non-specific cationic current (Ih). Our experiments showed that there was a correlation between the availability of the h-current and the spontaneous activity of the pyramidal cells, suggesting that this conductance acts as a pacemaker current in these neurones. Immunocytochemical experiments were also conducted on freshly isolated pyramidal cells to demonstrate the possible subunit composition of the channels responsible for the genesis of the pyramidal h-current. These investigations indicated the presence of HCN1, HCN2 and HCN4 subunits in the pyramidal cells.Received 15 May 2003; received after revision 26 June 2003; accepted 21 July 2003 相似文献
4.
Modification of ligand-gated receptor function at the postsynaptic domain is one of the most important mechanisms by which
the efficacy of synaptic transmission in the nervous system is regulated. Traditionally, these types of modifications have
been thought to be achieved mainly by altering the channel-gating properties or conductance of the receptors. However, recent
evidence suggests that AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxayolepropionic acid)-type ligand-gated glutamate receptors are continuously recycling between
the plasma membrane and the intracellular compartments via vesicle-mediated plasma membrane insertion and clathrin-dependent
endocytosis. Regulation of either receptor insertion or endocytosis results in a rapid change in the number of these receptors
expressed on the plasma membrane surface and in the receptor-mediated responses, thereby playing an important role in mediating
certain forms of synaptic plasticity. Thus, controlling the number of postsynaptic receptors by regulating the intracellular
trafficking and plasma membrane expression of the postsynaptic receptors may be a common and important mechanism of synaptic
plasticity in the mammalian central nervous system. 相似文献
5.
Yvonne G. J. van Helden Roger W. L. Godschalk Hans J. M. Swarts Peter C. H. Hollman Frederik J. van Schooten Jaap Keijer 《Cellular and molecular life sciences : CMLS》2011,68(3):489-504
Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray
gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1
−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1
−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1
−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1
−/− mice, which had, unlike wild-type (Bcmo1
+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence
lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after
BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice. 相似文献
6.
David J. Koss Benjamin D. Drever Sandra Stoppelkamp Gernot Riedel Bettina Platt 《Cellular and molecular life sciences : CMLS》2013,70(14):2585-2601
Several genetically engineered models exist that mimic aspects of the pathological and cognitive hallmarks of Alzheimer’s disease (AD). Here we report on a novel mouse model generated by targeted knock-in of transgenes containing mutated human amyloid precursor protein (APP) and microtubule-associated protein tau genes, inserted into the HPRT locus and controlled by the CaMKIIα regulatory element. These mice were crossed with an asymptomatic presenilin1A246E overexpressing line to generate PLB1Triple mice. Gene expression analysis and in situ hybridization confirmed stable, forebrain-specific, and gene-dose-dependent transgene expression. Brain tissue harvested from homozygous, heterozygous, and wild-type cohorts aged between 3 and 24 months was analyzed immunohistochemically and electrophysiologically. Homozygous PLB1Triple offspring presented with mostly intracellular cortical and hippocampal human APP/amyloid, first detected reliably at 6 months. Human tau was already uncovered at 3 months (phospho-tau at 6 months) and labeling intensifying progressively with age. Gene-dose dependence was confirmed in age-matched heterozygous females that accumulated less tau and amyloid protein. General excitability of hippocampal neurones was not altered in slices from PLB1Triple mice up to 12 months, but 2-year-old homozygous PLB1Triple mice had smaller synaptically evoked postsynaptic potentials compared with wild types. Synaptic plasticity (paired-pulse depression/facilitation and long-term potentiation) of synaptic CA1 pyramidal cell responses was deficient from 6 months of age. Long-term depression was not affected at any age or in any genotype. Therefore, despite comparatively subtle gene expression and protein build-up, PLB1Triple mice develop age-dependent progressive phenotypes, suggesting that aggressive protein accumulation is not necessary to reconstruct endophenotypes of AD. 相似文献
7.
Massicotte G 《Cellular and molecular life sciences : CMLS》2000,57(11):1542-1550
Long-term potentiation (LTP) and long-term depression (LTD) are two electrophysiological models that have been studied extensively in recent years as they may represent basic mechanisms in many neuronal networks to store certain types of information. In several brain regions, it has been shown that these two forms of synaptic plasticity require sufficient dendritic depolarization, with the amplitude of the calcium signal being crucial for the generation of either LTP or LTD. The rise in calcium concentration mediated by the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to stimulate various calcium-dependent enzymatic processes that could convert the induction signal into long-lasting changes in synaptic structure; protein kinases and phosphatases have so far been considered predominantly with regard to LTP and LTD formation. According to several lines of experimental evidence, changes in synaptic function observed with LTP and LTD are thought to be the result of modifications of postsynaptic currents mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors. Moreover, it has become apparent recently that activation of the calcium-dependent enzyme phospholipase A2 (PLA2) could be part of the molecular mechanisms involved in alterations of AMPA receptor properties during long-term changes in synaptic operation. In the present review, we will first describe the results that indicate a critical role of the phospholipases in regulating synaptic function. Next, sections will be devoted to the effects of PLA2 and phospholipids on the binding properties of glutamate receptors, and a revised biochemical model will be presented as an attempt to integrate the PLA2 enzyme into the mechanisms ( in particular kinases and phosphatases) that participate in adaptive neural plasticity. Finally, we will review data relevant to the issue of selective changes in AMPA binding after environmental enrichment and LTP. 相似文献
8.
M. F. Shi J. Jiao W. G. Lu F. Ye D. Ma Q. G. Dong X. Xie 《Cellular and molecular life sciences : CMLS》2010,67(22):3915-3925
Cancer stem cells (CSCs) play an important role in the development, invasion, and drug resistance of carcinoma, but the exact
phenotype and characteristics of ovarian CSCs are still disputable. In this study, we identified cancer stem cell-like cells
(CSC-LCs) and investigated their characteristics from the ovarian adenocarcinoma cell line 3AO. Our results showed that CSC-LCs
were enriched in sphere-forming test and highly expressed CD44+CD24−. The spheres and CD24− cells possessed strong tumorigenic ability by transplantation into nonobese diabetic/severe combined immunodeficient mice.
CD44+CD24− cells expressed stem cell markers and differentiated to CD44+CD24+ cells by immunofluorescence assay and fluorescence-activated cell-sorting analysis. In vitro experiments verified that CD44+CD24− cells were markedly resistant to carboplatin and paclitaxol. In conclusion, our study identifies the CD44+CD24− phenotype, self-renewal, high tumorigenicity, differentiation potential, and drug resistance of ovarian CSC-LCs. Our findings
may provide the evidence needed to explore a new strategy in the treatment of ovarian cancer. 相似文献
9.
Porcelli AM Ghelli A Mastrocola T Rugolo M 《Cellular and molecular life sciences : CMLS》1999,56(1-2):167-173
The Ca2+ ionophore ionomycin induced cytosolic [Ca2+]i elevation as well as strong activation of Cl− efflux in mouse mammary epithelial cell lines expressing wild-type or mutated (deletion of phenylalaline 508) cystic fibrosis
transmembrane conductance regulator (CFTR) or vector. Ionomycin-induced Cl− efflux was abolished by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, whereas both activators and inhibitors of phospholipase A2 had no effect, indicating the involvement of Ca2+-dependent Cl- channels. Stimulation of arachidonic acid release by ionomycin and phorbol ester was not significantly different between
wild-type or mutated cell lines, whereas vector-transfected cells exhibited a significant higher release, which was shown
to be due to larger amount of immunoreactive cytosolic phospholipase A2. These results indicate that phospholipase A2 activity of C127 cells was not influenced by the presence of wild-type or mutated CFTR.
Received 27 April 1999; received after revision 11 June 1999; accepted 23 July 1999 相似文献
10.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated pore loop channels. HCN channels are unique among
vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization.
In addition, voltage-dependent opening of these channels is directly regulated by the binding of cAMP. HCN channels are encoded
by four genes (HCN1–4) and are widely expressed throughout the heart and the central nervous system. The current flowing through
HCN channels, designated Ih or If, plays a key role in the control of cardiac and neuronal rhythmicity (“pacemaker current”). In addition, Ih contributes to several other neuronal processes, including determination of resting membrane potential, dendritic integration
and synaptic transmission. In this review we give an overview on structure, function and regulation of HCN channels. Particular
emphasis will be laid on the complex roles of these channels for neuronal function and cardiac rhythmicity.
Received 22 August 2008; received after revision 22 September 2008; accepted 24 September 2008 相似文献
11.
Diversity of Cl− Channels 总被引:5,自引:0,他引:5
Cl− channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis
of molecular biologic findings, ligand-gated Cl− channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed
by bestrophin and possibly by tweety, which encode Ca2+-activated Cl− channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential,
excitation, cellvolume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The
molecular structure of Cl− channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl− channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or
unidentified hydrophobic membrane proteins. Thus, novel Cl−-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic
and pathophysiologic roles.
Received 28 July 2005; received after revision 25 August 2005; accepted 21 September 2005 相似文献
12.
Maria C. Shina Annette Müller-Taubenberger Can Ünal Michael Schleicher Michael Steinert Ludwig Eichinger Rolf Müller Rosemarie Blau-Wasser Gernot Glöckner Angelika A. Noegel 《Cellular and molecular life sciences : CMLS》2011,68(2):303-313
Dictyostelium discoideum harbors a short (CRN12) and a long coronin (CRN7) composed of one and two beta-propellers, respectively. They are primarily
present in the cell cortex and cells lacking CRN12 (corA
−) or CRN7 (corB
−) have defects in actin driven processes. We compared the characteristics of a mutant cell line (corA
−
/corB
−) lacking CRN12 and CRN7 with the single mutants focusing on cytokinesis, phagocytosis, chemotaxis and development. Cytokinesis,
uptake of small particles, and developmental defects were not enhanced in the corA
−
/corB
− strain as compared to the single mutants, whereas motility and phagocytosis of yeast particles were more severely impaired.
It appears that although both proteins affect the same processes they do not act in a redundant manner. Rather, they often
act antagonistically, which is in accordance with their proposed roles in the actin cytoskeleton where CRN12 acts in actin
disassembly whereas CRN7 stabilizes actin filaments and protects them from disassembly. 相似文献
13.
In renal carcinoma cells (RCC4) hypoxia inducible factor-1 (HIF-1) is constitutively expressed due to a von Hippel Lindau
protein deficiency, but can be degraded by calpain, independently of the 26S proteasome, when exposed to hypoxia/nitric oxide
(NO). In this study we examined molecular mechanisms to explain calpain activation. The inability of hypoxia/NO to degrade
HIF-1α in respiratory-deficient RCC4-ρ0 cells pointed to the requirement for mitochondria-derived reactive oxygen species.
A prerequisite for O
2
−
in combination with NO to destabilize HIF-1α was corroborated in RCC4-p0 cells, when the redox cycler 2,3-dimethoxy-1,4-naphthoquinone
was used as a source of superoxide. Degradation of HIF-1α required intracellular calcium transients and calpain activation.
Using uric acid to interfere with signal transmission elicited by NO/O
2
−
blocked HIF-1α degradation and attenuated a calcium increase. We conclude that an oxidative signal as a result of NO/O
2
−
coformation triggers a calcium increase that activates calpain to degrade HIF-1α, independently of the proteasome.
Received 14 August 2007; received after revision 4 October 2007; accepted 22 October 2007 相似文献
14.
Parameshwaran K Buabeid MA Karuppagounder SS Uthayathas S Thiruchelvam K Shonesy B Dityatev A Escobar MC Dhanasekaran M Suppiramaniam V 《Cellular and molecular life sciences : CMLS》2012,69(5):829-841
In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of
neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted
when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure
has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular
mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral,
neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on
the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third
day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like
effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission,
and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in
protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845)
GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could
result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes. 相似文献
15.
Binglin Zhu Lige Zhao Dong Luo Demei Xu Tao Tan Zhifang Dong Ying Tang Zhuo Min Xiaojuan Deng Fei Sun Zhen Yan Guojun Chen 《Cellular and molecular life sciences : CMLS》2018,75(13):2473-2488
Furin is a proprotein convertase implicated in a variety of pathological processes including neurodegenerative diseases. However, the role of furin in neuronal plasticity and learning and memory remains to be elucidated. Here, we report that in brain-specific furin transgenic (Furin-Tg) mice, the dendritic spine density and proliferation of neural progenitor cells were significantly increased. These mice exhibited enhanced long-term potentiation (LTP) and spatial learning and memory performance, without alterations of miniature excitatory/inhibitory postsynaptic currents. In the cortex and hippocampus of Furin-Tg mice, the ratio of mature brain-derived neurotrophic factor (mBDNF) to pro-BDNF, and the activities of extracellular signal-related kinase (ERK) and cAMP response element-binding protein (CREB) were significantly elevated. We also found that hippocampal knockdown of CREB diminished the facilitation of LTP and cognitive function in Furin-Tg mice. Together, our results demonstrate that furin enhances dendritic morphogenesis and learning and memory in transgenic mice, which may be associated with BDNF–ERK–CREB signaling pathway. 相似文献
16.
Cancer cell metabolism is characterized by limited oxidative phosphorylation in order to minimize oxidative stress. We have
previously shown that the flavonoid flavone in HT-29 colon cancer cells increases the uptake of pyruvate or lactate into mitochondria,
which is followed by an increase in O2−.. production that finally leads to apoptosis. Similarly, a supply of palmitoylcarnitine in combination with carnitine induces
apoptosis in HT-29 cells by increasing the mitochondrial respiration rate. Here we show that flavone-induced apoptosis is
increased more than twofold in the presence of palmitoylcarnitine due to increased mitochondrial fatty acid transport and
the subsequent metabolic generation of O2−. in mitochondria is the initiating factor for the execution of apoptosis.
Received 12 August 2005; received after revision 12 October 2005; accepted 14 October 2005 相似文献
17.
J. -P. Bargetzi 《Cellular and molecular life sciences : CMLS》1958,14(12):445-447
Summary Two closely related forms ofCoregonus from Lake Neuchatel were examined cytologically and biochemically, in order to ascertain the chromosome number and the DNA
content of haploid and diploid nuclei.Coregonus fera has 2N=78 ± 2 chromosomes, and a DNA content (diploid) of 5.8 × 10−9 mg;Coregonus macrophthalmus, 2N=78+ ± 3, DNA content of 6.1 × 10−9 mg. The difference between the two DNA constants is statistically significant. These results do not support the hypothesis
which postulates that polyploidy may be a determining factor in the speciation of these fishes.
相似文献
18.
Hosseinkhani S 《Cellular and molecular life sciences : CMLS》2011,68(7):1167-1182
Firefly luciferase-catalyzed reaction proceeds via the initial formation of an enzyme-bound luciferyl adenylate intermediate.
The chemical origin of the color modulation in firefly bioluminescence has not been understood until recently. The presence
of the same luciferin molecule, in combination with various mutated forms of luciferase, can emit light at slightly different
wavelengths, ranging from red to yellow to green. A historical perspective of development in understanding of color emission
mechanism is presented. To explain the variation in the color of the bioluminescence, different factors have been discussed
and five hypotheses proposed for firefly bioluminescence color. On the basis of recent results, light-color modulation mechanism
of firefly luciferase propose that the light emitter is the excited singlet state of OL− [1(OL−)*], and light emission from 1(OL−)* is modulated by the polarity of the active-site environment at the phenol/phenolate terminal of the benzothiazole fragment
in oxyluciferin. 相似文献
19.
Qiang Zhang Yanfeng Li Lei Zhang Nan Yang Jiao Meng Pingping Zuo Yong Zhang Jie Chen Li Wang Xiang Gao Dahai Zhu 《Cellular and molecular life sciences : CMLS》2013,70(1):153-165
Changes in the structure and number of synapses modulate learning, memory and cognitive disorders. Ubiquitin-mediated protein modification is a key mechanism for regulating synaptic activity, though the precise control of this process remains poorly understood. RING finger protein 13 (RNF13) is a recently identified E3 ubiquitin ligase, and its in vivo function remains completely unknown. We show here that genetic deletion of RNF13 in mice leads to a significant deficit in spatial learning as determined by the Morris water maze test and Y-maze learning test. At the ultrastructral level, the synaptic vesicle density was decreased and the area of the active zone was increased at hippocampal synapses of RNF13-null mice compared with those of wild-type littermates. We found no change in the levels of SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex proteins in the hippocampus of RNF13-null mice, but impaired SNARE complex assembly. RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function. 相似文献
20.
Summary Octopamine and proctolin at concentrations below 10–8 M reversibly induce a spontaneous rhythmic depolarization which occurs in body-wall muscles ofLucilia larvae. The effect appears to be postsynaptic and mediated by receptors specific for each substance.This work was supported by NIEHS grant No. ES00814 and EPA grant No. R804345. 相似文献