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Article: Regulation of sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/β-catenin (CATNB) signaling pathway: An in vitro and in vivo study

TitleRegulation of sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/β-catenin (CATNB) signaling pathway: An in vitro and in vivo study
Authors
Keywordsβ-catenin
Adherens junction
Anchoring junction
N-cadherin
Nitric oxide
Nitric oxide synthase
Spermatogenesis
Testis
Issue Date2005
PublisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/
Citation
Biology Of Reproduction, 2005, v. 73 n. 3, p. 458-471 How to Cite?
AbstractDuring spermatogenesis, extensive restructuring of cell junctions takes place in the seminiferous epithelium to facilitate germ cell movement. However, the mechanism that regulates this event remains largely unknown. Recent studies have shown that nitric oxide (NO) likely regulates tight junction (TJ) dynamics in the testis via the cGMP/protein kinase G (cGMP-dependent protein kinase, PRKG) signaling pathway. Due to the proximity of TJ and adherens junctions (AJ) in the testis, in particular at the blood-testis barrier, it is of interest to investigate if NO can affect AJ dynamics. Studies using Sertoli-germ cell cocultures in vitro have shown that the levels of NOS (nitric oxide synthase), cGMP, and PRKG were induced when anchoring junctions were being established. Using an in vivo model in which adult rats were treated with adjudin [a molecule that induces adherens junction disruption, formerly called AF-2364, 1-(2,4-dichlorobenzyl)-IH-indazole-3-carbohydrazide], the event of AJ disruption was also associated with a transient iNOS (inducible nitric oxide synthase, NOS2) induction. Immunohistochemistry has illustrated that NOS2 was intensely accumulated in Sertoli and germ cells in the epithelium during adjudin-induced germ cell loss, with a concomitant accumulation of intracellular cGMP and an induction of PRKG but not cAMP or protein kinase A (cAMP-dependent protein kinase, PRKA). To identify the NOS-mediated downstream signaling partners, coimmunoprecipitation was used to demonstrate that NOS2 and eNOS (endothelial nitric oxide synthase, NOS3) were structurally associated with the N-cadherin (CDH2)/β-catenin (CATNB)/actin complex but not the nectin-3 (poliovirus receptor-related 3, PVRL 3)/afadin (myeloid/lymphoid or mixed lineage-leukemia tranlocation to 4 homolog, MLLT4) nor the integrin β1 (ITβ1)-mediated protein complexes, illustrating the spatial vicinity of NOS with selected AJ-protein complexes. Interestingly, CDH2 and CATNB were shown to dissociate from NOS during the adjudin-mediated AJ disruption, implicating the CDH2/CATNB protein complex is the likely downstream target of the NO signaling. Furthermore, PRKG, the downstream signaling protein of NOS, was shown to interact with CATNB in the rat testis. Perhaps the most important of all, pretreatment of testes with KT5823, a specific PRKG inhibitor, can indeed delay the adjudin-induced germ cell loss, further validating NOS/NO regulates Sertoli-germ cell AJ dynamics via the cGMP/PRKG pathway. These results illustrate that the CDH2/CATNB-mediated adhesion function in the testis is regulated, at least in part, via the NOS/cGMP/PRKG/CATNB pathway. © 2005 by the Society for the Study of Reproduction, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/143471
ISSN
2015 Impact Factor: 3.471
2015 SCImago Journal Rankings: 1.646
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, NPYen_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorWong, CHen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2011-12-02T05:19:13Z-
dc.date.available2011-12-02T05:19:13Z-
dc.date.issued2005en_HK
dc.identifier.citationBiology Of Reproduction, 2005, v. 73 n. 3, p. 458-471en_HK
dc.identifier.issn0006-3363en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143471-
dc.description.abstractDuring spermatogenesis, extensive restructuring of cell junctions takes place in the seminiferous epithelium to facilitate germ cell movement. However, the mechanism that regulates this event remains largely unknown. Recent studies have shown that nitric oxide (NO) likely regulates tight junction (TJ) dynamics in the testis via the cGMP/protein kinase G (cGMP-dependent protein kinase, PRKG) signaling pathway. Due to the proximity of TJ and adherens junctions (AJ) in the testis, in particular at the blood-testis barrier, it is of interest to investigate if NO can affect AJ dynamics. Studies using Sertoli-germ cell cocultures in vitro have shown that the levels of NOS (nitric oxide synthase), cGMP, and PRKG were induced when anchoring junctions were being established. Using an in vivo model in which adult rats were treated with adjudin [a molecule that induces adherens junction disruption, formerly called AF-2364, 1-(2,4-dichlorobenzyl)-IH-indazole-3-carbohydrazide], the event of AJ disruption was also associated with a transient iNOS (inducible nitric oxide synthase, NOS2) induction. Immunohistochemistry has illustrated that NOS2 was intensely accumulated in Sertoli and germ cells in the epithelium during adjudin-induced germ cell loss, with a concomitant accumulation of intracellular cGMP and an induction of PRKG but not cAMP or protein kinase A (cAMP-dependent protein kinase, PRKA). To identify the NOS-mediated downstream signaling partners, coimmunoprecipitation was used to demonstrate that NOS2 and eNOS (endothelial nitric oxide synthase, NOS3) were structurally associated with the N-cadherin (CDH2)/β-catenin (CATNB)/actin complex but not the nectin-3 (poliovirus receptor-related 3, PVRL 3)/afadin (myeloid/lymphoid or mixed lineage-leukemia tranlocation to 4 homolog, MLLT4) nor the integrin β1 (ITβ1)-mediated protein complexes, illustrating the spatial vicinity of NOS with selected AJ-protein complexes. Interestingly, CDH2 and CATNB were shown to dissociate from NOS during the adjudin-mediated AJ disruption, implicating the CDH2/CATNB protein complex is the likely downstream target of the NO signaling. Furthermore, PRKG, the downstream signaling protein of NOS, was shown to interact with CATNB in the rat testis. Perhaps the most important of all, pretreatment of testes with KT5823, a specific PRKG inhibitor, can indeed delay the adjudin-induced germ cell loss, further validating NOS/NO regulates Sertoli-germ cell AJ dynamics via the cGMP/PRKG pathway. These results illustrate that the CDH2/CATNB-mediated adhesion function in the testis is regulated, at least in part, via the NOS/cGMP/PRKG/CATNB pathway. © 2005 by the Society for the Study of Reproduction, Inc.en_HK
dc.languageengen_US
dc.publisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/en_HK
dc.relation.ispartofBiology of Reproductionen_HK
dc.subjectβ-cateninen_HK
dc.subjectAdherens junctionen_HK
dc.subjectAnchoring junctionen_HK
dc.subjectN-cadherinen_HK
dc.subjectNitric oxideen_HK
dc.subjectNitric oxide synthaseen_HK
dc.subjectSpermatogenesisen_HK
dc.subjectTestisen_HK
dc.subject.meshAdherens Junctionsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCarbazolesen_US
dc.subject.meshCells - Cultureden_US
dc.subject.meshCyclic GMPen_US
dc.subject.meshCyclic GMP - Dependent Protein Kinasesen_US
dc.subject.meshCytoskeletal Proteinsen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHydrazinesen_US
dc.subject.meshIndazolesen_US
dc.subject.meshIndolesen_US
dc.subject.meshMaleen_US
dc.subject.meshNitric Oxide Synthaseen_US
dc.subject.meshProtein Kinase Inhibitorsen_US
dc.subject.meshRNA - Messengeren_US
dc.subject.meshRatsen_US
dc.subject.meshRats - Sprague - Dawleyen_US
dc.subject.meshSertoli Cellsen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshSpermatozoaen_US
dc.subject.meshTrans - Activatorsen_US
dc.subject.meshbeta Cateninen_US
dc.titleRegulation of sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/β-catenin (CATNB) signaling pathway: An in vitro and in vivo studyen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, NPY: nikkilee@hku.hken_HK
dc.identifier.authorityLee, NPY=rp00263en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1095/biolreprod.105.040766en_HK
dc.identifier.pmid15858215-
dc.identifier.scopuseid_2-s2.0-23844545574en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-23844545574&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume73en_HK
dc.identifier.issue3en_HK
dc.identifier.spage458en_HK
dc.identifier.epage471en_HK
dc.identifier.isiWOS:000231369200009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, NPY=7402722690en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridWong, CH=8849630400en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK

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