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Article: Targeted and reversible disruption of the blood-testis barrier by an FSH mutant-occludin peptide conjugate

TitleTargeted and reversible disruption of the blood-testis barrier by an FSH mutant-occludin peptide conjugate
Authors
Issue Date2007
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
Faseb Journal, 2007, v. 21 n. 2, p. 438-448 How to Cite?
AbstractThe blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in mammals. As such, it poses a challenge to deliver any drugs to the seminiferous epithelium of the testis, such as a nonhormonal male contraceptive. To circumvent this problem, a genetically engineered follicle-stimulating hormone (FSH) mutant protein was produced in Spodoptera furgiperda (Sf)-9 insect cells to serve as a testis-specific carrier. Subsequently, a 22-amino acid peptide corresponding to the second extracellular loop of occludin, which was known to disrupt BTB integrity in vivo, was inserted to the FSH mutant by polymerase chain reaction (PCR), as well as chemical cross-linking. This molecule was found to have negligible hormonal activity but was still capable of binding to FSH receptors, which are restricted to Sertoli cells in mammals. When this FSH mutant-occludin peptide conjugate was administered to adult rats at 40 μg/adult rat (∼300 gm b.w.) via intraperitoneally (i.p.) injection, it induced transient and reversible disruption of the BTB, while at 150 μg/rat, it induced partial germ cell loss from the testis, particularly elongating/elongate spermatids. Most importantly, this effect was limited to the BTB without compromising the TJ-barrier integrity or cell adhesion in epithelia of other organs, such as kidney, liver, and small intestine. In summary, the use of an FSH mutant-occludin peptide conjugate is a feasible nanodevice to transiently compromise the BTB. © FASEB.
Persistent Identifierhttp://hdl.handle.net/10722/178980
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, CHen_US
dc.contributor.authorMruk, DDen_US
dc.contributor.authorLee, WMen_US
dc.contributor.authorCheng, CYen_US
dc.date.accessioned2012-12-19T09:51:13Z-
dc.date.available2012-12-19T09:51:13Z-
dc.date.issued2007en_US
dc.identifier.citationFaseb Journal, 2007, v. 21 n. 2, p. 438-448en_US
dc.identifier.issn0892-6638en_US
dc.identifier.urihttp://hdl.handle.net/10722/178980-
dc.description.abstractThe blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in mammals. As such, it poses a challenge to deliver any drugs to the seminiferous epithelium of the testis, such as a nonhormonal male contraceptive. To circumvent this problem, a genetically engineered follicle-stimulating hormone (FSH) mutant protein was produced in Spodoptera furgiperda (Sf)-9 insect cells to serve as a testis-specific carrier. Subsequently, a 22-amino acid peptide corresponding to the second extracellular loop of occludin, which was known to disrupt BTB integrity in vivo, was inserted to the FSH mutant by polymerase chain reaction (PCR), as well as chemical cross-linking. This molecule was found to have negligible hormonal activity but was still capable of binding to FSH receptors, which are restricted to Sertoli cells in mammals. When this FSH mutant-occludin peptide conjugate was administered to adult rats at 40 μg/adult rat (∼300 gm b.w.) via intraperitoneally (i.p.) injection, it induced transient and reversible disruption of the BTB, while at 150 μg/rat, it induced partial germ cell loss from the testis, particularly elongating/elongate spermatids. Most importantly, this effect was limited to the BTB without compromising the TJ-barrier integrity or cell adhesion in epithelia of other organs, such as kidney, liver, and small intestine. In summary, the use of an FSH mutant-occludin peptide conjugate is a feasible nanodevice to transiently compromise the BTB. © FASEB.en_US
dc.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/en_US
dc.relation.ispartofFASEB Journalen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntibodies - Blooden_US
dc.subject.meshBlood-Testis Barrier - Drug Effects - Metabolismen_US
dc.subject.meshCell Adhesion - Drug Effectsen_US
dc.subject.meshCyclic Amp - Metabolismen_US
dc.subject.meshEpithelium - Drug Effects - Metabolismen_US
dc.subject.meshFollicle Stimulating Hormone - Chemistry - Metabolism - Pharmacologyen_US
dc.subject.meshGerm Cells - Cytology - Drug Effects - Immunologyen_US
dc.subject.meshImmunoblottingen_US
dc.subject.meshInjections, Intraperitonealen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Proteins - Chemistry - Genetics - Pharmacologyen_US
dc.subject.meshMicroscopy, Electron, Transmissionen_US
dc.subject.meshMicroscopy, Fluorescenceen_US
dc.subject.meshMolecular Structureen_US
dc.subject.meshMutant Proteins - Chemistry - Metabolism - Pharmacologyen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReceptors, Fsh - Metabolismen_US
dc.subject.meshSpermatogenesisen_US
dc.subject.meshTestis - Cytology - Metabolism - Ultrastructureen_US
dc.titleTargeted and reversible disruption of the blood-testis barrier by an FSH mutant-occludin peptide conjugateen_US
dc.typeArticleen_US
dc.identifier.emailLee, WM: hrszlwm@hku.hken_US
dc.identifier.authorityLee, WM=rp00728en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1096/fj.05-4144comen_US
dc.identifier.pmid17167075-
dc.identifier.scopuseid_2-s2.0-33846786558en_US
dc.identifier.hkuros132224-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33846786558&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume21en_US
dc.identifier.issue2en_US
dc.identifier.spage438en_US
dc.identifier.epage448en_US
dc.identifier.isiWOS:000244686300017-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWong, CH=8849630400en_US
dc.identifier.scopusauthoridMruk, DD=6701823934en_US
dc.identifier.scopusauthoridLee, WM=24799156600en_US
dc.identifier.scopusauthoridCheng, CY=7404797787en_US

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