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- PMID: 17167075
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Article: Targeted and reversible disruption of the blood-testis barrier by an FSH mutant-occludin peptide conjugate
Title | Targeted and reversible disruption of the blood-testis barrier by an FSH mutant-occludin peptide conjugate |
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Authors | |
Keywords | Adherens junction Ectoplasmic specialization Male contraception Serfoli-germ cell interactions Spermatogenesis Tight junction |
Issue Date | 2007 |
Publisher | Federation 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? |
Abstract | The 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 Identifier | http://hdl.handle.net/10722/178980 |
ISSN | 2023 Impact Factor: 4.4 2023 SCImago Journal Rankings: 1.412 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wong, CH | en_US |
dc.contributor.author | Mruk, DD | en_US |
dc.contributor.author | Lee, WM | en_US |
dc.contributor.author | Cheng, CY | en_US |
dc.date.accessioned | 2012-12-19T09:51:13Z | - |
dc.date.available | 2012-12-19T09:51:13Z | - |
dc.date.issued | 2007 | en_US |
dc.identifier.citation | Faseb Journal, 2007, v. 21 n. 2, p. 438-448 | en_US |
dc.identifier.issn | 0892-6638 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/178980 | - |
dc.description.abstract | The 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.language | eng | en_US |
dc.publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/ | en_US |
dc.relation.ispartof | FASEB Journal | en_US |
dc.subject | Adherens junction | - |
dc.subject | Ectoplasmic specialization | - |
dc.subject | Male contraception | - |
dc.subject | Serfoli-germ cell interactions | - |
dc.subject | Spermatogenesis | - |
dc.subject | Tight junction | - |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Antibodies - Blood | en_US |
dc.subject.mesh | Blood-Testis Barrier - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Cell Adhesion - Drug Effects | en_US |
dc.subject.mesh | Cyclic Amp - Metabolism | en_US |
dc.subject.mesh | Epithelium - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Follicle Stimulating Hormone - Chemistry - Metabolism - Pharmacology | en_US |
dc.subject.mesh | Germ Cells - Cytology - Drug Effects - Immunology | en_US |
dc.subject.mesh | Immunoblotting | en_US |
dc.subject.mesh | Injections, Intraperitoneal | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Membrane Proteins - Chemistry - Genetics - Pharmacology | en_US |
dc.subject.mesh | Microscopy, Electron, Transmission | en_US |
dc.subject.mesh | Microscopy, Fluorescence | en_US |
dc.subject.mesh | Molecular Structure | en_US |
dc.subject.mesh | Mutant Proteins - Chemistry - Metabolism - Pharmacology | en_US |
dc.subject.mesh | Protein Binding | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, Sprague-Dawley | en_US |
dc.subject.mesh | Receptors, Fsh - Metabolism | en_US |
dc.subject.mesh | Spermatogenesis | en_US |
dc.subject.mesh | Testis - Cytology - Metabolism - Ultrastructure | en_US |
dc.title | Targeted and reversible disruption of the blood-testis barrier by an FSH mutant-occludin peptide conjugate | en_US |
dc.type | Article | en_US |
dc.identifier.email | Lee, WM: hrszlwm@hku.hk | en_US |
dc.identifier.authority | Lee, WM=rp00728 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1096/fj.05-4144com | en_US |
dc.identifier.pmid | 17167075 | - |
dc.identifier.scopus | eid_2-s2.0-33846786558 | en_US |
dc.identifier.hkuros | 132224 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-33846786558&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 21 | en_US |
dc.identifier.issue | 2 | en_US |
dc.identifier.spage | 438 | en_US |
dc.identifier.epage | 448 | en_US |
dc.identifier.isi | WOS:000244686300017 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Wong, CH=8849630400 | en_US |
dc.identifier.scopusauthorid | Mruk, DD=6701823934 | en_US |
dc.identifier.scopusauthorid | Lee, WM=24799156600 | en_US |
dc.identifier.scopusauthorid | Cheng, CY=7404797787 | en_US |
dc.identifier.issnl | 0892-6638 | - |