In JoVE (1)
Other Publications (11)
- Journal of Molecular Neuroscience : MN
- Science (New York, N.Y.)
- The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
- Fertility and Sterility
- Chemistry & Biodiversity
- Molecular Cell
- Trends in Pharmacological Sciences
- Journal of Neurochemistry
- Breast Cancer Research : BCR
- The Biochemical Journal
- BMC Cancer
Articles by Malka Cohen-Armon in JoVE
Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells Asher Castiel1, Leonid Visochek2,3, Leonid Mittelman4, Yael Zilberstein4, Francoise Dantzer5, Shai Izraeli1,6, Malka Cohen-Armon2,3 1Cancer Research Center, Sheba Medical Center, 2The Neufeld Cardiac Research Institute, Tel-Aviv University, 3Department of Physiology and Pharmacology, Tel-Aviv University, 4Imaging Unit, Sackler Faculty of Medicine, Tel-Aviv University, 5Biotechnology and Cell Signaling, Ecole Superieure de Biotechnologie Strasbourg, 6Department of Human Molecular Genetics and Biochemistry, Tel-Aviv University The cytotoxic activity of the phenanthridine PJ-34 in cancer cells undergoing mitosis was documented in real time by live confocal imaging. PJ-34 eradicated human breast cancer MDA-MB-231 cells harboring extra-centrosomes in mitosis. Unlike normal bi-focal mitosis, the extra-centrosomes were not clustered in the two spindle poles in the presence of PJ-34.
Other articles by Malka Cohen-Armon on PubMed
Stimulation-induced Modifications in Go Proteins Examined in Giant Fused Synaptosomes Journal of Molecular Neuroscience : MN. Feb, 2003 | Pubmed ID: 12663937 Synaptoneurosomes (1-3 microm in diameter), prepared from rat brain stem or brain cortex, were fused with liposomes, producing a high yield of giant synaptosomes (10-60 microm in diameter). Single channel currents were measured by using the cell-attach patch-clamp technique. The membrane of the majority of these giant synaptosomes retained the cell membrane selective permeability. However, nonpermeating molecules, such as guanine nucleotides and antibodies directed against GTP-binding region in the alpha-subunit of trimeric GTP-binding proteins, were trapped in the giant synaptosomes during their preparation. Activation of Go proteins was assayed in high [K(+)]-depolarized giant synaptosomes, indicating the advantage of this preparation for tracing signal-transduction mechanisms in stimulated synaptic membranes. Stimulation-induced interactions between membrane proteins, either native or reconstituted, can be studied in the giant synaptosomes.
Long-term Memory Requires PolyADP-ribosylation Science (New York, N.Y.). Jun, 2004 | Pubmed ID: 15205535 PolyADP-ribose-polymerase 1 is activated in neurons that mediate several forms of long-term memory in Aplysia. Because polyADP-ribosylation of nuclear proteins is a response to DNA damage in virtually all eukaryotic cells, it is surprising that activation of the polymerase occurs during learning and is required for long-term memory. We suggest that fast and transient decondensation of chromatin structure by polyADP-ribosylation enables the transcription needed to form long-term memory without strand breaks in DNA.
PolyADP-ribosylation is Involved in Neurotrophic Activity The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Aug, 2005 | Pubmed ID: 16093393 PolyADP-ribosylation is a transient posttranslational modification of proteins, mainly catalyzed by poly(ADP-ribose)polymerase-1 (PARP-1). This highly conserved nuclear protein is activated rapidly in response to DNA nick formation and promotes a fast DNA repair. Here, we examine a possible association between polyADP-ribosylation and the activity of neurotrophins and neuroprotective peptides taking part in life-or-death decisions in mammalian neurons. The presented results indicate an alternative mode of PARP-1 activation in the absence of DNA damage by neurotrophin-induced signaling mechanisms. PARP-1 was activated in rat cerebral cortical neurons briefly exposed to NGF-related nerve growth factors and to the neuroprotective peptides NAP (the peptide NAPVSIPQ, derived from the activity-dependent neuroprotective protein ADNP) and ADNF-9 (the peptide SALLRSIPA, derived from the activity-dependent neurotrophic factor ADNF) In addition, polyADP-ribosylation was involved in the neurotrophic activity of NGF-induced and NAP-induced neurite outgrowth in differentiating pheochromocytoma 12 cells as well as in the neuroprotective activity of NAP in neurons treated with the Alzheimer's disease neurotoxin beta-amyloid. A fast loosening of the highly condensed chromatin structure by polyADP-ribosylation of histone H1, which renders DNA accessible to transcription and repair, may underlie the role of polyADP-ribosylation in neurotrophic activity.
Role of Poly(ADP-ribosyl)ation During Human Spermatogenesis Fertility and Sterility. Nov, 2006 | Pubmed ID: 16996513 Genomic stability of cells is known to be linked to their poly(ADP-ribosyl)ation capacity. We aimed to demonstrate, for the first time, the patterns of poly(ADP-ribosyl)ation during human spermatogenesis.
A Fatal Effect of Hornet Venom on Rat-brain Cortical Neurons Chemistry & Biodiversity. May, 2006 | Pubmed ID: 17193289 In a previous study, it was shown that the hornet venom or, more specifically, its venom sac extract (VSE) possesses deoxyribonuclease activity that exerts an effect both on insects as well as on mammals. We have now examined the effect of hornet VSE on primary culture of rat cortical neurons. Judging on the basis of our results, VSE induces a rapid cell death by a) permeabilizing the cell membrane, b) inducing DNA breaks, and c) cleaving the nuclear protein poly-ADP-ribose polymerase (PARP-1), thereby preventing DNA repair.
DNA-independent PARP-1 Activation by Phosphorylated ERK2 Increases Elk1 Activity: a Link to Histone Acetylation Molecular Cell. Jan, 2007 | Pubmed ID: 17244536 PolyADP-ribose polymerases (PARPs) catalyze a posttranslational modification of nuclear proteins by polyADP-ribosylation. The catalytic activity of the abundant nuclear protein PARP-1 is stimulated by DNA strand breaks, and PARP-1 activation is required for initiation of DNA repair. Here we show that PARP-1 also acts within extracellular signal-regulated kinase (ERK) signaling cascade that mediates growth and differentiation. The findings reveal an alternative mode of PARP-1 activation, which does not involve binding to DNA or DNA damage. In a cell-free system, recombinant PARP-1 was intensively activated and thereby polyADP-ribosylated by a direct interaction with phosphorylated ERK2, and the activated PARP-1 dramatically increased ERK2-catalyzed phosphorylation of the transcription factor Elk1. In cortical neurons treated with nerve growth factors and in stimulated cardiomyocytes, PARP-1 activation enhanced ERK-induced Elk1-phosphorylation, core histone acetylation, and transcription of the Elk1-target gene c-fos. These findings constitute evidence for PARP-1 activity within the ERK signal-transduction pathway.
PARP-1 Activation in the ERK Signaling Pathway Trends in Pharmacological Sciences. Nov, 2007 | Pubmed ID: 17950909 PARP-1 is a highly conserved DNA-binding protein, the most abundant member of the polyADP-ribose polymerases (PARP) family, which catalyzes post-translational modification of proteins by polyADP-ribosylation. This modification affects protein-protein and protein-DNA interactions. Binding of PARP-1 to breakages in damaged DNA causes its activation and auto-polyADP-ribosylation in a process that is pivotal for DNA repair. Our recent findings outlined an alternative mechanism of PARP-1 activation via a direct interaction with phosphorylated ERK2 (externally regulated kinase), which is unrelated to DNA damage and does not involve PARP-1 binding to DNA. Furthermore, ERK2-induced PARP-1 activation dramatically amplifies ERK-signals, enhancing ERK-induced phosphorylation of the transcription factor Elk1 and enhancing core histone acetylation and expression of the Elk1 target gene, c-fos. Thus, PARP-1 activation in the ERK signaling pathway mediates epigenetic mechanisms promoting growth, proliferation and differentiation regulated by the Raf-MEK-ERK phosphorylation cascade.
PolyADP-ribosylation is Required for Long-term Memory Formation in Mammals Journal of Neurochemistry. Oct, 2009 | Pubmed ID: 19645746 PolyADP-ribosylation is a post-translational modification of nuclear proteins, catalyzed by polyADP-ribose polymerases (PARPs). In the nucleus, polyADP-ribosylation catalyzed by PARP-1 alters protein-protein and protein-DNA interactions, and is implicated in chromatin remodeling, DNA transcription, and repair. Previous results linked the activation of PARP-1 with long-term memory formation during learning in the marine mollusk Aplysia ( Science 2004, 304:1820-1822). Furthermore, PARP-1 was highly activated in mammalian cerebral neurons treated with neurotrophins and neurotrophic peptides promoting neurite outgrowth and synaptic plasticity. Here, we examine the possibility that PARP-1 activation is required for memory formation during learning in mammals. Mice were tested in two learning paradigms, object recognition and fear conditioning. PolyADP-ribosylation of PARP-1 and histone H1 were detected in their cerebral cortex and hippocampus immediately after their training session. Moreover, in both behavioral paradigms, suppression of PARP activity in the CNS during learning impaired their long-term memory formation, without damaging their short-term memory. These findings implicate PARP-1 activation in molecular processes underlying long-term memory formation during learning.
A Selective Eradication of Human Nonhereditary Breast Cancer Cells by Phenanthridine-derived PolyADP-ribose Polymerase Inhibitors Breast Cancer Research : BCR. 2009 | Pubmed ID: 19891779 PARP-1 (polyADP-ribose polymerase-1) is known to be activated in response to DNA damage, and activated PARP-1 promotes DNA repair. However, a recently disclosed alternative mechanism of PARP-1 activation by phosphorylated externally regulated kinase (ERK) implicates PARP-1 in a vast number of signal-transduction networks in the cell. Here, PARP-1 activation was examined for its possible effects on cell proliferation in both normal and malignant cells.
Ca2+-induced PARP-1 Activation and ANF Expression Are Coupled Events in Cardiomyocytes The Biochemical Journal. Sep, 2011 | Pubmed ID: 21635224 The nuclear protein PARP-1 [poly(ADP-ribose) polymerase-1] is activated in cardiomyocytes exposed to hypoxia causing DNA breaks. Unlike this stress-induced PARP-1 activation, our results provide evidence for Ca(2+)-induced PARP-1 activation in contracting newborn cardiomyocytes treated with growth factors and hormones that increased their contraction rate, induced intracellular Ca(2+) mobilization and its rhythmical and transient translocation into the nucleus. Furthermore, activated PARP-1 up-regulated the activity of phosphorylated ERK (extracellular-signal-regulated kinase) in the nucleus, promoting expression of the Elk1 target gene c-fos. Up-regulation of the transcription factor c-Fos/GATA-4 promoted ANF (atrial natriuretic factor) expression. Given that expression of ANF is known to be implicated in morphological changes, growth and development of cardiomyocytes, these results outline a PARP-1-dependent signal transduction mechanism that links contraction rate and Ca(2+) mobilization with the expression of genes underlying morphological changes in cardiomyocytes.
A Phenanthrene Derived PARP Inhibitor is an Extra-centrosomes De-clustering Agent Exclusively Eradicating Human Cancer Cells BMC Cancer. 2011 | Pubmed ID: 21943092 Cells of most human cancers have supernumerary centrosomes. To enable an accurate chromosome segregation and cell division, these cells developed a yet unresolved molecular mechanism, clustering their extra centrosomes at two poles, thereby mimicking mitosis in normal cells. Failure of this bipolar centrosome clustering causes multipolar spindle structures and aberrant chromosomes segregation that prevent normal cell division and lead to 'mitotic catastrophe cell death'.