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Full-Text Articles in Education

Pkc Inhibition Increases Gap Junction Intercellular Communication And Cell Adhesion In Human Neuroblastoma, M. Morley, C. Jones, M. Sidhu, V. Gupta, S. Bernier, W. Rushlow, Daniel Belliveau Dec 2009

Pkc Inhibition Increases Gap Junction Intercellular Communication And Cell Adhesion In Human Neuroblastoma, M. Morley, C. Jones, M. Sidhu, V. Gupta, S. Bernier, W. Rushlow, Daniel Belliveau

Daniel J. Belliveau

Abstract Gap junction intercellular communication and cell–cell adhesion are essential for maintaining a normal cellular phenotype, including the control of growth and proliferation. Loss of either cell–cell adhesion or communication is common in cancers, while restoration of function is associated with tumor suppression. Protein kinase C (PKC) isozymes regulate a broad spectrum of cellular functions including growth and proliferation, and their overexpression has been correlated with carcinogenesis. Consequently, PKC inhibitors are currently undergoing clinical trials as an anti-cancer agents although the precise cellular alterations induced by PKC inhibitors remain to be elucidated. In the current study, the effects ...


Connexin Overexpression Differentially Suppresses Glioma Growth And Contributes To The Bystander Effect Following Hsv-Thymidine Kinase Gene Therapy, T. Jiminez, W. Fox, C. Naus, J. Galipeau, Daniel Belliveau Dec 2005

Connexin Overexpression Differentially Suppresses Glioma Growth And Contributes To The Bystander Effect Following Hsv-Thymidine Kinase Gene Therapy, T. Jiminez, W. Fox, C. Naus, J. Galipeau, Daniel Belliveau

Daniel J. Belliveau

Neoplastic transformation is frequently associated with a loss of gap junctional intercellular communication and reduced expression of connexins. The introduction of connexin genes into tumor cells reverses the proliferative characteristics of such cells. However, there is very little comparative information on the effects of different connexins on cancer cell growth. We hypothesized that Cx26, Cx32, or Cx43 would display differential growth suppression of C6 glioma cells and uniquely modulate the bystander effect following transduction of C6 cells with HSVtk followed by suicide gene therapy. The bystander phenomenon is the death of a greater number of tumor cells than are expressing ...


Enhanced Neurite Outgrowth In Pc12 Cells Mediated By Connexin Hemichannels And Atp, Daniel Belliveau, M. Bani-Yagoub, R. Mcgirr, C. Naus, W. Rushlow Dec 2005

Enhanced Neurite Outgrowth In Pc12 Cells Mediated By Connexin Hemichannels And Atp, Daniel Belliveau, M. Bani-Yagoub, R. Mcgirr, C. Naus, W. Rushlow

Daniel J. Belliveau

Gap junctions have traditionally been described as transmembrane channels that facilitate intercellular communication via the passage of small molecules. Connexins, the basic building blocks of gap junctions, are expressed in most mammalian tissues including the developing and adult central nervous system. During brain development, connexins are temporally and spatially regulated suggesting they play an important role in the proper formation of the central nervous system. In the current study, connexins 32 and 43 were overexpressed in PC12 cells to determine whether connexins are involved in neuronal differentiation. Both connexin 32 and 43 were appropriately trafficked to the cell membrane following ...


Changes In Calcineurin Expression Induced In The Rat Brain By The Administration Of Antipsychotics, W. Rushlow, Y. Seah, Daniel Belliveau, N. Rajakumar Dec 2004

Changes In Calcineurin Expression Induced In The Rat Brain By The Administration Of Antipsychotics, W. Rushlow, Y. Seah, Daniel Belliveau, N. Rajakumar

Daniel J. Belliveau

Calcineurin (CN) was recently identified as a susceptibility gene for schizophrenia as well as showing altered RNA expression levels in the post-mortem brains of individuals with schizophrenia. CN knockout mice show a number of behaviours associated with schizophrenia, including deficits in sensorimotor gating, suggesting a link between CN and psychosis. Concurrently, we found, using genome screening techniques, that antipsychotics alter CN expression levels. Therefore, western blotting, in situ hybridization, immunocytochemistry and phosphatase assays were employed to determine what effect antipsychotics have on CN. The results indicate that clozapine, risperidone and haloperidol cause substantial reductions in the A subunit of CN ...


Nerve Growth Factor Increases Connexin43 Phosphorylation And Gap Junctional Intercellular Communication, P. Cushing, R. Bhalla, A. Johnson, W. Rushlow, S. Meakin, Daniel Belliveau Dec 2004

Nerve Growth Factor Increases Connexin43 Phosphorylation And Gap Junctional Intercellular Communication, P. Cushing, R. Bhalla, A. Johnson, W. Rushlow, S. Meakin, Daniel Belliveau

Daniel J. Belliveau

The function of gap junctions is regulated by the phosphorylation state of their connexin subunits. Numerous growth factors are known to regulate connexin phosphorylation; however, the effect of nerve growth factor on gap junction function is not understood. The phosphorylation of connexin subunits is a key event during many aspects of the lifecycle of a connexin, including open/close states, assembly/trafficking, and degradation, and thus affects the functionality of the channel. PC12 cells infected with connexin43 (Cx43) retrovirus were used as a neuronal model to characterize the signal transduction pathways activated by nerve growth factor (NGF) that potentially affect ...


Retroviral Delivery Of Connexin Genes To Human Breast Tumor Cells Inhibits In Vivo Tumor Growth By A Mechanism That Is Independent Of Significant Gap Junctional Intercellular Communication, H. Qin, Q. Shao, H. Curtis, J. Galipeau, Daniel Belliveau, T. Wang, M. Alaoui-Jamali, D. Laird Dec 2001

Retroviral Delivery Of Connexin Genes To Human Breast Tumor Cells Inhibits In Vivo Tumor Growth By A Mechanism That Is Independent Of Significant Gap Junctional Intercellular Communication, H. Qin, Q. Shao, H. Curtis, J. Galipeau, Daniel Belliveau, T. Wang, M. Alaoui-Jamali, D. Laird

Daniel J. Belliveau

The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast tumor cells were found to exhibit diverse gap junction phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of Cx43 and sparse intercellular communication (MDA-MB-231); and (c) significant levels of Cx43 and moderate intercellular communication (Hs578T). Although retroviral delivery of Cx43 and Cx26 cDNAs to MDA-MB-231 cells did not achieve an expected substantial rescue of intercellular communication, overexpression of connexin genes did result in a dramatic suppression of tumor growth when connexin-expressing MDA-MB-231 cells were ...


Aggregated Dsred-Tagged Cx43 And Over-Expressed Cx43 Are Targeted To Lysosomes In Human Breast Cancer Cells, H. Qin, Q. Shao, Daniel Belliveau, D. Laird Dec 2000

Aggregated Dsred-Tagged Cx43 And Over-Expressed Cx43 Are Targeted To Lysosomes In Human Breast Cancer Cells, H. Qin, Q. Shao, Daniel Belliveau, D. Laird

Daniel J. Belliveau

To investigate if either wild-type or aggregated Cx43 is abnormally targeted to lysosomes in human breast tumor cells, we examined the fate of DsRed-tagged Cx43 and over-expressed Cx43 in communication-deficient HBL-100 and MDA-MB-231 cells. DsRed-tagged Cx43 was assembled into gap junctions in control normal rat kidney cells that express endogenous Cx43 but not in Cx43-negative HBL-100 cells. However, when HBL-100 cells were engineered to coexpress wild-type Cx43 a population of DsRed-tagged Cx43 was rescued and assembled into gap junctions. Co-expression of wild-type Cx26 failed to rescue the assembly of DsRed-tagged Cx43 into gap junctions. Immunolocalization studies revealed that DsRed-tagged Cx43 ...


Viral Shedding And Biodistribution Of G207, A Multimutated, Conditionally Replicating Herpes Simplex Virus Type 1, After Intracerebral Inoculation In Aotus, T. Todo, F. Feigenbaum, S. Rabkin, F. Lakeman, J. Newsome, P. Johnson, E. Mitchell, Daniel Belliveau, J. Ostrove, R. Martuza Dec 1999

Viral Shedding And Biodistribution Of G207, A Multimutated, Conditionally Replicating Herpes Simplex Virus Type 1, After Intracerebral Inoculation In Aotus, T. Todo, F. Feigenbaum, S. Rabkin, F. Lakeman, J. Newsome, P. Johnson, E. Mitchell, Daniel Belliveau, J. Ostrove, R. Martuza

Daniel J. Belliveau

G207 is a multimutated, conditionally replicating herpes simplex virus type 1 (HSV-1) that is currently in clinical trial for patients with malignant glioma. G207 exhibits an efficient oncolytic activity in tumor cells, yet minimal toxicity in normal tissue when injected into the brains of HSV-susceptible mice or nonhuman primates. In this study, we evaluated the shedding and biodistribution of clinical-grade G207 after intracerebral inoculation (3 × 107 pfu) in four New World owl monkeys (Aotus nancymae). Using PCR analyses and viral cultures, neither infectious virus nor viral DNA was detected from tear, saliva, or vaginal secretion samples at any time point ...


Autocrine Hepatocyte Growth Factor Provides A Local Mechanism For Promoting Axonal Growth, X. Yang, J. Toma, S. Bamji, Daniel Belliveau, J. Kohn, M. Park, F. Miller Dec 1997

Autocrine Hepatocyte Growth Factor Provides A Local Mechanism For Promoting Axonal Growth, X. Yang, J. Toma, S. Bamji, Daniel Belliveau, J. Kohn, M. Park, F. Miller

Daniel J. Belliveau

In this report, we describe a novel local mechanism necessary for optimal axonal growth that involves hepatocyte growth factor (HGF). Sympathetic neurons of the superior cervical ganglion coexpress bioactive HGF and its receptor, the Met tyrosine kinase, both in vivo and in vitro. Exogenous HGF selectively promotes the growth but not survival of cultured sympathetic neurons; the magnitude of this growth effect is similar to that observed with exogenous NGF. Conversely, HGF antibodies that inhibit endogenous HGF decrease sympathetic neuron growth but have no effect on survival. This autocrine HGF is required locally by sympathetic axons for optimal growth, as ...


Differential Expression Of Gap Junctions In Neurons And Astrocytes Dervied From P19 Embryonal Carcinoma Cells, Daniel Belliveau, J. Bechberger, K. Rodgers, C. Naus Dec 1996

Differential Expression Of Gap Junctions In Neurons And Astrocytes Dervied From P19 Embryonal Carcinoma Cells, Daniel Belliveau, J. Bechberger, K. Rodgers, C. Naus

Daniel J. Belliveau

The P19 embryonal carcinoma cell line represents a pluripotential stem cell that can differentiate along the neural or muscle cell lineage when exposed to different environments. Exposure to retinoic acid induces P19 cells to differentiate into neurons and astrocytes that express similar developmental markers as their embryonic counterparts. We examined the expression of gap junction genes during differentiation of these stem cells into neurons and astrocytes. Untreated P19 cells express at least two gap junction proteins, connexins 26 and 43. Connexin32 could not be detected in these cells. Treatment for 96 hr with 0.3 mM retinoic acid induced the ...


Blocking Nerve Growth Factor Binding To The P75 Neurotrophin Receptor On Sympathetic Neurons Transiently Reduces Trka Activation But Does Not Affect Neuronal Survival, C. Lachance, Daniel Belliveau, P. Barker Dec 1996

Blocking Nerve Growth Factor Binding To The P75 Neurotrophin Receptor On Sympathetic Neurons Transiently Reduces Trka Activation But Does Not Affect Neuronal Survival, C. Lachance, Daniel Belliveau, P. Barker

Daniel J. Belliveau

Nerve growth factor interacts with the trkA tyrosine kinase receptor and with the p75 neurotrophin receptor. It is clear that trkA mediates most, if not all, of the stereotypical responses of sympathetic neurons to nerve growth factor but the role of the p75 neurotrophin receptor is unclear. In this study, we have asked whether a functional interaction between p75 neurotrophin receptor and trkA exists in primary sympathetic neurons by disrupting nerve growth factor binding to p75 neurotrophin receptor. Acute assays reveal that blocking antibodies directed against p75 neurotrophin receptor reduce nerve growth factor-mediated trkA tyrosine phosphorylation and reduce the amount ...


Transgenic Mice Expressing The Intracellular Domain Of The P75 Neurotrophin Receptor Undergo Neuronal Apoptosis, M. Majdan, C. Lachance, A. Gloster, R. Aloyz, C. Zeindler, S. Bamji, A. Bhakar, Daniel Belliveau, J. Fawcett, F. Miller, P. Barker Dec 1996

Transgenic Mice Expressing The Intracellular Domain Of The P75 Neurotrophin Receptor Undergo Neuronal Apoptosis, M. Majdan, C. Lachance, A. Gloster, R. Aloyz, C. Zeindler, S. Bamji, A. Bhakar, Daniel Belliveau, J. Fawcett, F. Miller, P. Barker

Daniel J. Belliveau

We have asked whether p75NTR may play a role in neuronal apoptosis by producing transgenic mice that express the p75NTR intracellular domain within peripheral and central neurons. These animals showed profound reductions in numbers of sympathetic and peripheral sensory neurons as well as cell loss in the neocortex, where there is normally little or no p75NTR expression. Developmental loss of facial motor neurons was not observed, but induced expression of the p75NTR intracellular domain within adult animals led to increased motor neuron death after axotomy. Biochemical analyses suggest that these effects were not attributable to a p75NTR-dependent reduction in trk ...


Ngf And Neurotrophin-3 Both Activate Trka On Sympathetic Neurons But Differentially Regulate Survival And Neuritogenesis, Daniel Belliveau, I. Krivko, C. Lachance, J. Kohn, D. Rusakov, D. Kaplan, F. Miller Dec 1996

Ngf And Neurotrophin-3 Both Activate Trka On Sympathetic Neurons But Differentially Regulate Survival And Neuritogenesis, Daniel Belliveau, I. Krivko, C. Lachance, J. Kohn, D. Rusakov, D. Kaplan, F. Miller

Daniel J. Belliveau

In this report we examine the biological and molecular basis of the control of sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3). NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth-associated genes in NGF-dependent sympathetic neurons, but it is 20-40-fold less efficient in supporting their survival. Both NT-3 and NGF induce similar sustained, long-term activation of TrkA, while NGF is 10-fold more efficient than NT-3 in mediating acute, short-term TrkA activity. At similar acute levels of TrkA activation, NT-3 still mediates neuronal survival two- to threefold less well than NGF. However, a mutant NT-3 ...


Adenovirus-Mediated Gene Transfer Of The Tumor Suppressor, P53, Induces Apoptosis In Postmitotic Neurons, R. Slack, Daniel Belliveau, M. Rosenberg, J. Atwal, H. Lochmuller, R. Aloyz, A. Haghighi, B. Lach, P. Seth, E. Cooper, F. Miller Dec 1995

Adenovirus-Mediated Gene Transfer Of The Tumor Suppressor, P53, Induces Apoptosis In Postmitotic Neurons, R. Slack, Daniel Belliveau, M. Rosenberg, J. Atwal, H. Lochmuller, R. Aloyz, A. Haghighi, B. Lach, P. Seth, E. Cooper, F. Miller

Daniel J. Belliveau

Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found ...


Cellular Localization Of Gap Junction Mrnas In Developing Rat Brain, Daniel Belliveau, C. Naus Dec 1994

Cellular Localization Of Gap Junction Mrnas In Developing Rat Brain, Daniel Belliveau, C. Naus

Daniel J. Belliveau

We investigated the developmental expression and cellular resolution of connexin32 and 43 mRNA in the rat brain using in situ hybridization. Utilizing 35S-labelled probes, in situ hybridization was performed on sections of embryonic day 20 and postnatal days 3, 10, 15, 30 and adult brain. Connexin32 mRNA was first detected in brainstem nuclei at postnatal day 3 and in the midbrain at postnatal day 15. The level of this message continued to increase to postnatal day 30 where the level of message reached a plateau or slightly decreased by adulthood. The distribution of signal included the medial vestibular nucleus, dorsal ...


Cortical Type 2 Astrocytes Are Not Dye Coupled Nor Do They Express The Major Gap Junction Genes Found In The Central Nervous System, Daniel Belliveau, C. Naus Dec 1993

Cortical Type 2 Astrocytes Are Not Dye Coupled Nor Do They Express The Major Gap Junction Genes Found In The Central Nervous System, Daniel Belliveau, C. Naus

Daniel J. Belliveau

The O‐2A progenitor cell first described from the rat optic nerve is a bipotential precursor of oligodendrocytes and type 2 astrocytes. Each cell expresses specific markers that distinguish them as unique cell types. O‐2A progenitors cultured in high serum preferentially differntiate into type 2 astrocytes and when exposed to defined medium or low serum develop along the oligodendrocyte lineage. We analyzed the gap junction gene expression of type 2 astrocytes to determine if they are coupled to form a syncytium, like their type 1 astrocyte counterparts. Dye coupling experiments demonstrated that cortical type 2 astrocytes are not coupled ...


In Vivo Growth Of C6 Glioma Cells Transfected With Connexin43 Cdna, C. Naus, K. Elisevich, D. Zhu, Daniel Belliveau, R. Del Maestro Dec 1991

In Vivo Growth Of C6 Glioma Cells Transfected With Connexin43 Cdna, C. Naus, K. Elisevich, D. Zhu, Daniel Belliveau, R. Del Maestro

Daniel J. Belliveau

In order to examine the possible role of intercellular communication via gap junctions in the control of tumor growth, we have transfected C6 glioma cells with connexin43 cDNA. We obtained several clones with variable expression of connexin43. The growth rate of these clones in culture was inversely related to the degree of expression of the transfected cDNA. To examine the growth of these transfected cells in vivo, cells were grown in spinner culture flasks to form spheroids 250–300 µm in diameter. Spheroids of nontransfected C6 cells produced large gliomas. Immunohistochemical and in situ hybridization analyses revealed relatively high levels ...


Regulation Of Connexin32 And Connexin43 Mrna And Protein During Neural Development, Daniel Belliveau, G. Kidder, C. Naus Dec 1990

Regulation Of Connexin32 And Connexin43 Mrna And Protein During Neural Development, Daniel Belliveau, G. Kidder, C. Naus

Daniel J. Belliveau

No abstract provided.


Regional Differences In Connexin32 And Connexin43 Messenger Rnas In Rat Brain, C. Naus, Daniel Belliveau, J. Bechberger Dec 1989

Regional Differences In Connexin32 And Connexin43 Messenger Rnas In Rat Brain, C. Naus, Daniel Belliveau, J. Bechberger

Daniel J. Belliveau

The regional distribution of gap junction mRNAs was examined in the adult rat brain. The level of connexin43 mRNA is more abundant than connexin32, being homogeneously distributed throughout different regions of brain. In contrast, there is dramatic heterogeneity in the level of connexin32 mRNA, with the highest level in the hindbrain. These results suggest that the gap junction genes are differentially expressed in regions of the adult rat brain.