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Distribution of exogenous metallothionein following intraperitoneal and intramuscular injection of metallothionein-deficient mice
Citation
Lewis, KE and Chung, RS and West, AK and Chuah, MI, Distribution of exogenous metallothionein following intraperitoneal and intramuscular injection of metallothionein-deficient mice, Histology and histopathology, 27, (11) pp. 1459-1470. ISSN 0213-3911 (2012) [Refereed Article]
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Copyright Statement
Copyright 2012 Histology and histopathology
Official URL: http://www.hh.um.es/
Abstract
Metallothionein-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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | MT-I/II-knockout mice, MT-IIA injection, urinary system, liver, brain |
| Research Division: | Biological Sciences |
| Research Group: | Biochemistry and Cell Biology |
| Research Field: | Systems Biology |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding Knowledge |
| Objective Field: | Expanding Knowledge in the Medical and Health Sciences |
| Author: | Lewis, KE (Miss Katherine Lewis) |
| Author: | Chung, RS (Associate Professor Roger Chung) |
| Author: | West, AK (Professor Adrian West) |
| Author: | Chuah, MI (Dr Inn Chuah) |
| ID Code: | 81546 |
| Year Published: | 2012 |
| Web of Science® Times Cited: | 6 |
| Deposited By: | Medicine (Discipline) |
| Deposited On: | 2012-12-13 |
| Last Modified: | 2014-12-17 |
| Downloads: | 1 View Download Statistics |
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