High transcytosis of melanotransferrin (P97) across the blood-brain barrier - Université d'Artois Access content directly
Journal Articles Journal of Neurochemistry Year : 2002

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

Julie Poirier
  • Function : Author
Julie Jodoin
  • Function : Author
Yanick Bertrand
  • Function : Author
Richard R. Desrosiers
  • Function : Author
Claude Dagenais
  • Function : Author
Michel Demeule
  • Function : Author
Tran Nguyen
  • Function : Author
Julie Lanthier
  • Function : Author
Reinhard Gabathuler
  • Function : Author
Malcolm Kennard
  • Function : Author
Wilfred A. Jefferies
  • Function : Author
Delara Karkan
  • Function : Author
Sam Tsai
  • Function : Author

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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Dates and versions

hal-00526740 , version 1 (15-10-2010)

Identifiers

  • HAL Id : hal-00526740 , version 1

Cite

Julie Poirier, Julie Jodoin, Yanick Bertrand, Richard R. Desrosiers, Claude Dagenais, et al.. High transcytosis of melanotransferrin (P97) across the blood-brain barrier. Journal of Neurochemistry, 2002, 83, p. 924-933. ⟨hal-00526740⟩

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