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Distribution of exogenous metallothionein following intraperitoneal and intramuscular injection of metallothionein-deficient mice

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dc.contributor.authorLewis, Katherine E. Lewis
dc.contributor.authorChung, Roger S.
dc.contributor.authorWest, Adrian K.
dc.contributor.authorChuah, Meng Inn
dc.date.accessioned2017-11-08T16:31:56Z
dc.date.available2017-11-08T16:31:56Z
dc.date.issued2012
dc.description.abstractMetallothionein-I/II (MT-I/II) is a small metal-binding protein with antioxidant and neuroprotective properties, which has been used experimentally as a neurotherapeutic agent in multiple conditions. Therefore it is important to determine whether exogenous MT-I/II is retained in specific organs or expelled from the body following intramuscular and intraperitoneal injection. The distribution of exogenous MT-IIA (the major human MT-I/II isoform) was examined in MT-I/II-deficient mice, by immunohistochemistry of tissue samples and western blotting of urine samples. MT-IIA was detected within epithelial cells of the kidney cortical and medullary tubules within 1 hour of either intramuscular or intraperitoneal injection. Additionally, MT-IIA was detected within the urine at 1 hour after injection, indicating rapid absorbance into the circulation and filtration through the kidney glomerulus. A portion of the intramuscularly-injected MT-IIA remained within the muscle for at least 24 hours after injection. No MT-IIA was observed within the liver or the brain after either a single injection or a series of MT-IIA injections. These results are consistent with earlier reports that exogenously administered MT-IIA does not cross the intact blood-brain barrier, although a receptor for MT-I/II (megalin) is present in the choroid plexus. We postulate that due to losses through the urine, circulating MT-IIA levels drop rapidly after injection and do not permit transport across the choroid plexus. Peptide analogues of MT-I/II with similar neuroactive properties (emtins) may be more suited for CNS delivery.es
dc.formatapplication/pdfes
dc.format.extent12es
dc.identifier.citationHistology and histopathology, Vol. 27, n.º 11 (2012)
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/54464
dc.languageenges
dc.publisherF. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectMT-I/II-knockout micees
dc.subjectMT-IIA injectiones
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísicaes
dc.titleDistribution of exogenous metallothionein following intraperitoneal and intramuscular injection of metallothionein-deficient micees
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.27, nº11 (2012)