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Cited by 221

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High transcytosis of melanotransferrin (P97) across the blood–brain barrier

Demeule, Michel, Poirier, Julie, Jodoin, Julie, Bertrand, Yanick, Desrosiers, Richard R., Dagenais, Claude, Nguyen, Tran, Lanthier, Julie, Gabathuler, Reinhard, Kennard, Malcolm, Jefferies, Wilfred A., Karkan, Delara, Tsai, Sam, Fenart, Laurence, Cecchelli, Roméo, Béliveau, Richard·2002·Journal of Neurochemistry

Abstract

The blood–brain barrier (BBB) performs a neuroprotective function by tightly controlling access to the brain; consequently it also impedes access of proteins as well as pharmacological agents to cerebral tissues. We demonstrate here that recombinant human melanotransferrin (P97) is highly accumulated into the mouse brain following intravenous injection and in situ brain perfusion. Moreover, P97 transcytosis across bovine brain capillary endothelial cell (BBCEC) monolayers is at least 14‐fold higher than that of holo‐transferrin, with no apparent intra‐endothelial degradation. This high transcytosis of P97 was not related to changes in the BBCEC monolayer integrity. In addition, the transendothelial transport of P97 was sensitive to temperature and was both concentration‐ and conformation‐dependent, suggesting that the transport of P97 is due to receptor‐mediated endocytosis. In spite of the high degree of sequence identity between P97 and transferrin, a different receptor than the one for transferrin is involved in P97 transendothelial transport. A member of the low‐density lipoprotein receptor protein family, likely LRP, seems to be involved in P97 transendothelial transport. The brain accumulation, high rate of P97 transcytosis and its very low level in the blood suggest that P97 could be advantageously employed as a new delivery system to target drugs directly to the brain.

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Metadata

Authors
Demeule, M., Poirier, J., Jodoin, J., Bertrand, Y., Desrosiers, R. R., Dagenais, C., Nguyen, T., Lanthier, J., Gabathuler, R., Kennard, M., Jefferies, W. A., Karkan, D., Tsai, S., Fenart, L., Cecchelli, R., & Béliveau, R.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2002-11
Volume
83
Issue
4
Pages
924-933
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W1598970150
Cited by
221
References
1
FWCI
5.96
Type
journal article
Language
en
Open access
closed

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Demeule, M., Poirier, J., Jodoin, J., Bertrand, Y., Desrosiers, R. R., Dagenais, C., Nguyen, T., Lanthier, J., Gabathuler, R., Kennard, M., Jefferies, W. A., Karkan, D., Tsai, S., Fenart, L., Cecchelli, R., & Béliveau, R. (2002). High transcytosis of melanotransferrin (P97) across the blood–brain barrier. Journal of Neurochemistry. https://doi.org/10.1046/j.1471-4159.2002.01201.x

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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