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Article: A c-Src Inhibitor Peptide Based on Connexin43 Exerts Neuroprotective Effects through the Inhibition of Glial Hemichannel Activity.

Gangoso, Ester / Talaverón, Rocío / Jaraíz-Rodríguez, Myriam / Domínguez-Prieto, Marta / Ezan, Pascal / Koulakoff, Annette / Medina, José M / Giaume, Christian / Tabernero, Arantxa

Frontiers in molecular neuroscience

2017 Volume 10, Page(s) 418

Abstract: The non-receptor tyrosine kinase c-Src is an important mediator in several signaling pathways ... promoted a transient increase in c-Src activity in reactive astrocytes surrounding the neuronal lesion ...

Abstract	The non-receptor tyrosine kinase c-Src is an important mediator in several signaling pathways related to neuroinflammation. Our previous study showed that cortical injection of kainic acid (KA) promoted a transient increase in c-Src activity in reactive astrocytes surrounding the neuronal lesion. As a cell-penetrating peptide based on connexin43 (Cx43), specifically TAT-Cx43
Language	English
Publishing date	2017-12-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452967-9
ISSN	1662-5099
ISSN	1662-5099
DOI	10.3389/fnmol.2017.00418
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Article ; Online: Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells.

Herrero-González, S / Gangoso, E / Giaume, C / Naus, C C / Medina, J M / Tabernero, A

Oncogene

2010 Volume 29, Issue 42, Page(s) 5712–5723

Abstract: ... through the upregulation of p21 and p27. Interestingly, connexin43 diminishes the oncogenic activity of c-Src exhibited ... for connexin43 to inhibit c-Src activity and cell proliferation. In conclusion, by acting as a substrate of c-Src ... an early step in the antiproliferative effects of connexin43. Although c-Src is known to phosphorylate ...

Abstract	One of the characteristics of gliomas is a decrease in the expression of connexin43, a protein that forms gap junctions. Restoring connexin43 expression in glioma cells reduces their exacerbated rate of cell growth, although it is not yet known how connexin43 modifies the expression of genes involved in cell proliferation. Here, we show that restoring connexin43 to C6 glioma cells impedes their progression from G0/G1 to the S phase of the cell cycle by reducing retinoblastoma phosphorylation and cyclin E expression through the upregulation of p21 and p27. Interestingly, connexin43 diminishes the oncogenic activity of c-Src exhibited by glioma cells. By studying a Tyr247 and Tyr265 mutant connexin43, we show that these residues are required for connexin43 to inhibit c-Src activity and cell proliferation. In conclusion, by acting as a substrate of c-Src, connexin43 reduces its oncogenic activity and decreases the rate of glioma cell proliferation, potentially an early step in the antiproliferative effects of connexin43. Although c-Src is known to phosphorylate connexin43, this study provides the first evidence that connexin43 can also inhibit c-Src activity.
MeSH term(s)	Animals ; Blotting, Western ; Cell Cycle/physiology ; Cell Line, Tumor ; Cell Proliferation ; Cell Separation ; Connexin 43/metabolism ; Flow Cytometry ; Gene Expression ; Gene Expression Regulation, Neoplastic/genetics ; Genes, src/genetics ; Glioma/genetics ; Glioma/metabolism ; Mutation ; RNA, Small Interfering ; Rats ; Transfection
Chemical Substances	Connexin 43 ; RNA, Small Interfering
Language	English
Publishing date	2010-10-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/onc.2010.299
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Article ; Online: Reduced connexin43 expression correlates with c-Src activation, proliferation, and glucose uptake in reactive astrocytes after an excitotoxic insult.

Gangoso, Ester / Ezan, Pascal / Valle-Casuso, José Carlos / Herrero-González, Sandra / Koulakoff, Annette / Medina, Jose M / Giaume, Christian / Tabernero, Arantxa

Glia

2012 Volume 60, Issue 12, Page(s) 2040–2049

Abstract: ... modified in reactive astrocytes. Downregulation of Cx43 in cultured astrocytes activates c-Src, promotes ... an increased glucose uptake. Previous in vitro studies reported that c-Src is the link between Cx43 and glucose ... uptake and proliferation in astrocytes. Here, we found that c-Src activity increased in the lesioned area ...

Abstract	In diverse brain pathologies, astrocytes become reactive and undergo profound phenotypic changes. Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes, is one of the proteins modified in reactive astrocytes. Downregulation of Cx43 in cultured astrocytes activates c-Src, promotes proliferation, and increases the rate of glucose uptake; however, so far there have been no studies examining whether this cascade of events takes place in reactive astrocytes. In this work, we analyzed this pathway after a cortical lesion induced by a kainic acid injection. As previously described, astrocytes reacted to the lesion with an increase in glial fibrillary acidic protein and a decrease in Cx43 expression. Some of these reactive astrocytes proliferated, as estimated by bromodeoxyuridine incorporation and cyclins D1 and D3 upregulation. In addition, the expression of the glucose transporter GLUT-3 and the enzyme responsible for glucose phosphorylation, Type II hexokinase (Hx-2), were induced in reactive astrocytes, suggesting an increased glucose uptake. Previous in vitro studies reported that c-Src is the link between Cx43 and glucose uptake and proliferation in astrocytes. Here, we found that c-Src activity increased in the lesioned area. c-Src activation and Cx43 downregulation preceded the peak of Hx-2 and cyclin D3 expression, suggesting that c-Src could mediate the effect of Cx43 on glucose uptake and proliferation in reactive astrocytes after an excitotoxic insult. Interestingly, we identify c-Src, GLUT-3, and Hx-2 in the signaling mechanisms involved in the reaction of astroglia to injury. Altogether these data contribute to identify new therapeutical targets to enhance astrocyte neuroprotective activities.
MeSH term(s)	Animals ; Astrocytes/drug effects ; Astrocytes/metabolism ; Astrocytes/pathology ; Cell Proliferation/drug effects ; Connexin 43/antagonists & inhibitors ; Connexin 43/biosynthesis ; Connexin 43/genetics ; Excitatory Amino Acid Agonists/toxicity ; Genes, src/physiology ; Glucose/metabolism ; Kainic Acid/toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic
Chemical Substances	Connexin 43 ; Excitatory Amino Acid Agonists ; Glucose (IY9XDZ35W2) ; Kainic Acid (SIV03811UC)
Language	English
Publishing date	2012-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639414-0
ISSN	1098-1136 ; 0894-1491
ISSN (online)	1098-1136
ISSN	0894-1491
DOI	10.1002/glia.22418
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Zs.A 2345: Show issues

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Article ; Online: Contribution of a neuroscience-informed approach for developing interventions for acute stress reaction.

Verdonk, Charles / Giaume, L / Trousselard, M

BMJ military health

2023

Language	English
Publishing date	2023-08-31
Publishing country	England
Document type	Letter
ZDB-ID	3011686-7
ISSN	2633-3775 ; 2633-3767
ISSN (online)	2633-3775
ISSN	2633-3767
DOI	10.1136/military-2023-002538
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Article ; Online: Glial Connexins and Pannexins in the Healthy and Diseased Brain.

Giaume, Christian / Naus, Christian C / Sáez, Juan C / Leybaert, Luc

Physiological reviews

2020 Volume 101, Issue 1, Page(s) 93–145

Abstract: Over the past several decades a large amount of data have established that glial cells, the main cell population in the brain, dynamically interact with neurons and thus impact their activity and survival. One typical feature of glia is their marked ... ...

Abstract	Over the past several decades a large amount of data have established that glial cells, the main cell population in the brain, dynamically interact with neurons and thus impact their activity and survival. One typical feature of glia is their marked expression of several connexins, the membrane proteins forming intercellular gap junction channels and hemichannels. Pannexins, which have a tetraspan membrane topology as connexins, are also detected in glial cells. Here, we review the evidence that connexin and pannexin channels are actively involved in dynamic and metabolic neuroglial interactions in physiological as well as in pathological situations. These features of neuroglial interactions open the way to identify novel non-neuronal aspects that allow for a better understanding of behavior and information processing performed by neurons. This will also complement the "neurocentric" view by facilitating the development of glia-targeted therapeutic strategies in brain disease.
MeSH term(s)	Animals ; Brain/physiology ; Brain Diseases/drug therapy ; Brain Diseases/physiopathology ; Connexins/physiology ; Gap Junctions/drug effects ; Gap Junctions/physiology ; Humans ; Neuroglia/physiology
Chemical Substances	Connexins
Language	English
Publishing date	2020-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00043.2018
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Article ; Online: Astroglial Wiring is Adding Complexity to Neuroglial Networking.

Giaume, Christian

Frontiers in neuroenergetics

2010 Volume 2

Abstract: Astrocytes are organized as networks of communicating cells due to their high expression level of connexins, the molecular constituents of gap junction channels. Based on their permeability properties for ions and small signaling molecules such ... ...

Abstract	Astrocytes are organized as networks of communicating cells due to their high expression level of connexins, the molecular constituents of gap junction channels. Based on their permeability properties for ions and small signaling molecules such astroglial wiring interferes with neuronal activity and survival. In this paper, I identify and discuss which future technical and conceptual progress or advances should be achieved in order to better understand how neuroglial networking contributes to brain functions and dysfunctions.
Language	English
Publishing date	2010-09-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2474552-2
ISSN	1662-6427 ; 1662-6427
ISSN (online)	1662-6427
ISSN	1662-6427
DOI	10.3389/fnene.2010.00129
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Article ; Online: Environmental control of rice flowering time.

Vicentini, Giulio / Biancucci, Marco / Mineri, Lorenzo / Chirivì, Daniele / Giaume, Francesca / Miao, Yiling / Kyozuka, Junko / Brambilla, Vittoria / Betti, Camilla / Fornara, Fabio

Plant communications

2023 Volume 4, Issue 5, Page(s) 100610

Abstract: Correct measurement of environmental parameters is fundamental for plant fitness and survival, as well as for timing developmental transitions, including the switch from vegetative to reproductive growth. Important parameters that affect flowering time ... ...

Abstract	Correct measurement of environmental parameters is fundamental for plant fitness and survival, as well as for timing developmental transitions, including the switch from vegetative to reproductive growth. Important parameters that affect flowering time include day length (photoperiod) and temperature. Their response pathways have been best described in Arabidopsis, which currently offers a detailed conceptual framework and serves as a comparison for other species. Rice, the focus of this review, also possesses a photoperiodic flowering pathway, but 150 million years of divergent evolution in very different environments have diversified its molecular architecture. The ambient temperature perception pathway is strongly intertwined with the photoperiod pathway and essentially converges on the same genes to modify flowering time. When observing network topologies, it is evident that the rice flowering network is centered on EARLY HEADING DATE 1, a rice-specific transcriptional regulator. Here, we summarize the most important features of the rice photoperiodic flowering network, with an emphasis on its uniqueness, and discuss its connections with hormonal, temperature perception, and stress pathways.
MeSH term(s)	Flowers/genetics ; Oryza/metabolism ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Photoperiod ; Circadian Rhythm/physiology ; Arabidopsis/genetics
Chemical Substances	Plant Proteins
Language	English
Publishing date	2023-05-04
Publishing country	China
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	2590-3462
ISSN (online)	2590-3462
DOI	10.1016/j.xplc.2023.100610
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Article ; Online: Introduction to the special issue: Dynamic and metabolic interactions between astrocytes and neurons.

Giaume, C / Oliet, S

Neuroscience

2016 Volume 323, Page(s) 1–2

MeSH term(s)	Animals ; Astrocytes/metabolism ; Neurons/metabolism
Language	English
Publishing date	2016-05-26
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2016.02.062
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Article ; Online ; Conference proceedings: Bridging the gap to therapeutic strategies based on connexin/pannexin biology.

Naus, Christian C / Giaume, Christian

Journal of translational medicine

2016 Volume 14, Issue 1, Page(s) 330

Abstract: A unique workshop was recently held focusing on enhancing collaborations leading to identify and update the development of therapeutic strategies targeting connexin/pannexin large pore channels. Basic scientists exploring the functions of these channels ... ...

Abstract	A unique workshop was recently held focusing on enhancing collaborations leading to identify and update the development of therapeutic strategies targeting connexin/pannexin large pore channels. Basic scientists exploring the functions of these channels in various pathologies gathered together with leading pharma companies which are targeting gap junction proteins for specific therapeutic applications. This highlights how paths of discovery research can converge with therapeutic strategies in innovative ways to enhance target identification and validation.
MeSH term(s)	Amino Acid Sequence ; Animals ; Connexins/chemistry ; Connexins/metabolism ; Disease ; Humans ; Molecular Targeted Therapy ; Nerve Tissue Proteins/chemistry ; Nerve Tissue Proteins/metabolism
Chemical Substances	Connexins ; Nerve Tissue Proteins
Language	English
Publishing date	2016-11-29
Publishing country	England
Document type	Congresses
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-016-1089-0
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Article: Acetylcholine-induced closure of gap junction channels in rat lacrimal glands is probably mediated by protein kinase C.

Randriamampita, C / Giaume, C / Neyton, J / Trautmann, A

Pflugers Archiv : European journal of physiology

1988 Volume 412, Issue 5, Page(s) 462–468

Abstract: ... of activators of protein kinase C on gap junction conductance measured with the double patch-clamp technique ... degrees C) to 25 microM OAG. After a prolonged OAG treatment, the ability of ACh to uncouple the cells was ...

Abstract	In rat lacrimal gland cells, application of acetylcholine (ACh) opens Ca-dependent channels and closes gap junction channels. We have shown previously that the increase in intracellular calcium concentration induced by ACh, is not required for the closure of gap junctions. We have examined the effects of activators of protein kinase C on gap junction conductance measured with the double patch-clamp technique. This conductance was markedly reduced by incubating the cell pairs for a few minutes with 100 nM phorbol dibutyrate (PdBu). Two membrane permeant analogues of diacylglycerol, OAG (1-oleoyl-2-acetyl-glycerol) and DOG (1,2-dioleoyl-glycerol) also induced a closure of gap junction channels. This effect was observed in the concentration range 10-100 microM when the diacylglycerol was added on intact cells, and at 75 microM when it was applied on dialysed cells. The cell uncoupling was not mediated by phosphatidate, a degradation product of OAG, nor by a phospholipase A2-induced increase in arachidonate concentration. The OAG-induced closure of gap junction channels reversed spontaneously upon prolonged exposure (more than 90 min at 37 degrees C) to 25 microM OAG. After a prolonged OAG treatment, the ability of ACh to uncouple the cells was markedly reduced. ACh induced uncoupling was modulated to some extent by intracellular Ca and had an absolute requirement for Mg. These results indicate that ACh-induced closure of gap junction channels may be mediated by PKC.
MeSH term(s)	Acetylcholine/metabolism ; Animals ; Diglycerides/pharmacology ; In Vitro Techniques ; Intercellular Junctions/drug effects ; Intercellular Junctions/physiology ; Lacrimal Apparatus/physiology ; Magnesium/physiology ; Phorbol 12,13-Dibutyrate/pharmacology ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/physiology ; Rats ; Rats, Inbred Strains
Chemical Substances	Diglycerides ; Phorbol 12,13-Dibutyrate (37558-16-0) ; 1-oleoyl-2-acetylglycerol (86390-77-4) ; Protein Kinase C (EC 2.7.11.13) ; Magnesium (I38ZP9992A) ; Acetylcholine (N9YNS0M02X) ; diolein (Z3MP1W91CW)
Language	English
Publishing date	1988-10
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/bf00582534
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