Antiepileptic teratogen valproic acid (VPA) modulates organisation and dynamics of the actin cytoskeleton

Walmod, Peter S.; Skladchikova, Galina; Kawa, Anna; Berezin, Vladimir; Bock, Elisabeth

doi:10.1002/(sici)1097-0169(1999)42:3<241::aid-cm7>3.0.co;2-3

Cited by 25 publications

(11 citation statements)

References 54 publications

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“…Winterwood et al concluded that integrin internalization is a key mechanism, necessary to control adhesion and migration dynamics of carcinoma cells, and, consequently, that high integrin surface expression impairs motile behaviour (22). According to this observation, VPA reduced the motility of murine fibrosarcoma L929 tumor cells, and the blocking of integrin ß1-binding sites counteracted the effects of VPA (23). Nevertheless, our data did not provide a consistent picture of the mode of action of VPA.…”

Section: Discussioncontrasting

confidence: 80%

Modulation of adhesion and growth of colon and pancreatic cancer cells by the histone deacetylase inhibitor valproic acid

Jones

1998

Int J Mol Med

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Abstract. Histone deacetylase (HDAC) inhibitors belong to a promising class of antineoplastic agents which affect tumor growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro on preclinical colon and pancreatic cancer models. Human colon adenocarcinoma HT-29 and pancreatic carcinoma DanG cells were treated with 1 mM VPA for different time periods during cell proliferation MTT assays, and to evaluate the tumor cell adhesion to endothelial cell monolayers. Alterations of ß1 integrin subunits (α1-6) were analyzed by flow cytometry and RT-PCR. VPA significantly caused growth arrest in tumor cells and prevented tumor cell attachment to the endothelium. HT-29 cell adhesion was blocked to a higher extent than the adhesion of DanG cells. VPA modified membranous integrin ß1 expression, quantity and quality (up-or down-regulation) which depended on the tumor type investigated. Furthermore, VPA diminished integrin coding mRNA in HT-29 but not in DanG cells. We conclude that VPA shifts the integrin ß1 subunit balance from a 'pathological' towards a 'physiological' expression pattern leading to reduced tumor growth and invasion. Further study is required to elucidate the molecular background of the post-transcriptional modifications of VPA in order to exploit the potential of this agent in the treatment of colon and pancreatic cancer.

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Section: Discussioncontrasting

confidence: 80%

Modulation of adhesion and growth of colon and pancreatic cancer cells by the histone deacetylase inhibitor valproic acid

Jones

1998

Int J Mol Med

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“…13. For double immunostaining for synaptophysin and GAP43, cell cultures were fixed in 4% w/v paraformaldehyde in sodium phosphate buffer (0.1 M NaH 2 PO 4 , 50 mM sucrose, 0.4 mM CaCl 2 , pH 7.1) for 30 min at room temperature, blocked with 10% v/v normal goat serum, 1% w/v BSA in phosphate-buffered saline for 1 h, and washed with 1% BSA containing 0.2% w/v saponin.…”

Section: Methodsmentioning

confidence: 99%

A Synthetic Peptide Ligand of Neural Cell Adhesion Molecule (NCAM), C3d, Promotes Neuritogenesis and Synaptogenesis and Modulates Presynaptic Function in Primary Cultures of Rat Hippocampal Neurons

Kiryushko

Kofoed²,

Skladchikova³

et al. 2003

Journal of Biological Chemistry

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The neural cell adhesion molecule (NCAM) plays a key role in morphogenesis of the nervous system and in remodeling of neuronal connections accompanying regenerative and cognitive processes. Recently, a new synthetic ligand of NCAM, the C3-peptide, which binds to the NCAM IgI module, has been identified by means of combinatorial chemistry (Rønn, L. C. B, Olsen, M., Ostergaard, S., Kiselyov, V., Berezin, V., Mortensen, M. T., Lerche, M. H., Jensen, P. H., Soroka, V., Saffell, J. L., Doherty, P., Poulsen, F. M., Bock, E., Holm, A., and Saffells, J. L. (1999) Nat. Biotechnol. 17, 1000 -1005). In vitro, the dendrimeric form of C3, termed C3d, disrupts NCAM-mediated cell adhesion, induces neurite outgrowth, and triggers intracellular signaling cascades similar to those activated by homophilic NCAM binding. The peptide may therefore be expected to regulate regeneration and synaptic plasticity. Here we demonstrate that in primary cultures of hippocampal neurons: 1) C3d induces a sustained neuritogenic response, the neuritogenic activity of the compound being dependent on the dose, starting time, and duration of peptide application; 2) the peptide triggers the neuritogenic response by forming an adhesive substratum necessary for NCAM-mediated neurite formation and elongation; 3) C3d promotes synapse formation; and 4) C3d modulates the presynaptic function, causing a transient increase of the function at low (2 and 5 M) doses and a reduction when applied at a higher concentration (10 M). The effect of the peptide is dependent on the activation of the fibroblast growth factor receptor. We suggest that C3d may constitute a useful lead for the development of compounds for treatment of various neurodegenerative disorders. The neural cell adhesion molecule (NCAM)1 plays a key role in morphogenesis of the nervous system (2) and in remodeling of neuronal connections associated with regenerative and cognitive processes (for review, see Ref.3). The extracellular part of NCAM binds to a variety of ligands, the most important being the NCAM molecule itself. Homophilic NCAM binding is thought to involve the first five immunoglobulin (IgI-IgV) modules of NCAM with a double reciprocal interaction between the IgI and IgII modules of two interacting NCAM molecules (4, 5). Upon homophilic NCAM binding, intracellular signaling cascades, including the Ras-mitogen-activated protein kinase (Ras-MAPK) and phospholipase C␥-associated pathways, are activated (6), resulting in neurite outgrowth. Antibody interventive studies have shown NCAM necessary for the induction and maintenance of long term potentiation and for stable memory retention in vivo (7,8), suggesting that NCAM is involved in synaptic plasticity.The modulation of processes of neuronal differentiation and plasticity through NCAM has been impeded by the absence of small synthetic agonists mimicking homophilic or heterophilic interactions of NCAM. However, recently, a new synthetic ligand of NCAM, the C3-peptide, has been identified by means of combinatorial chemistry. The dendrimeric...

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“…VPA animals also present with a reduced number of spines in the prefrontal cortex, dorsal hippocampus and basolateral amygdala, but an increase in the dendritic spine density in accumbens and ventral hippocampus (Bringas et al, ; Raza et al, ). Related to these effects on dendrite morphology, VPA treatment has been shown to induce an increase of F‐actin affecting cell morphology (Walmod et al, ).…”

Section: Non‐genetic Autism Modelsmentioning

confidence: 99%

Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models

Martínez‐Cerdeño

2016

Developmental Neurobiology

200

127

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Dendrites and spines are the main neuronal structures receiving input from other neurons and glial cells. Dendritic and spine number, size and morphology are some of the crucial factors determining how signals coming from individual synapses are integrated. Much remains to be understood about the characteristics of neuronal dendrites and dendritic spines in autism and related disorders. Though there have been many studies conducted using autism mouse models, few have been carried out using postmortem human tissue from patients. Available animal models of autism include those generated thought genetic modifications and those non-genetic models of the disease. Here, we review how dendrite and spine morphology and number is affected in autism and related neurodevelopmental diseases, both in human, and genetic and non-genetic animal models of autism. Overall, data obtained from human and animal models point to a generalized reduction in the size and number together with an alteration of the morphology of dendrites; and an increase in spine densities with immature morphology, indicating a general spine immaturity state in autism. Additional human studies on dendrite and spine number and morphology in postmortem tissue are needed to understand the properties of these structures in the cerebral cortex of patients with autism.

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Antiepileptic teratogen valproic acid (VPA) modulates organisation and dynamics of the actin cytoskeleton

Cited by 25 publications

References 54 publications

Modulation of adhesion and growth of colon and pancreatic cancer cells by the histone deacetylase inhibitor valproic acid

Modulation of adhesion and growth of colon and pancreatic cancer cells by the histone deacetylase inhibitor valproic acid

A Synthetic Peptide Ligand of Neural Cell Adhesion Molecule (NCAM), C3d, Promotes Neuritogenesis and Synaptogenesis and Modulates Presynaptic Function in Primary Cultures of Rat Hippocampal Neurons

Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models

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