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Human & Experimental Toxicology, Vol. 26, No. 4, 295-302 (2007)
DOI: 10.1177/0960327107070496

Putative proteins involved in manganese transport across the blood-brain barr 1ier

Vanessa A Fitsanakis

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA

Greg Piccola

Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, USA

Ana Paula Marreilha dos Santos

Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

Judy L Aschner

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA

Michael Aschner

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA, michael.aschner{at}vanderbilt.edu, The Kennedy Center, Vanderbilt University Medical Center, Nashville, TN, USA

Manganese (Mn) is an essential nutrient required for proper growth and maintenance of numerous biological systems. At high levels it is known to be neurotoxic. While focused research concerning the transport of Mn across the blood-brain barrier (BBB) is on-going, the exact identity of the transporter(s) responsible is still debated. The transferrin receptor (TfR) and the divalent metal transporter-1 (DMT-1) have long been thought to play a role in brain Mn deposition. However, evidence suggests that Mn may also be transported by other proteins. One model system of the BBB, rat brain endothelial (RBE4) cells, are known to express many proteins suspected to be involved in metal transport. This review will discuss the biological importance of Mn, and then briefly describe several proteins that may be involved in transport of this metal across the BBB. The latter section will examine the potential usefulness of RBE4 cells in characterizing various aspects of Mn transport, and basic culture techniques involved in working with these cells. It is hoped that ideas put forth in this article will stimulate further investigations into the complex nature of Mn transport, and address the importance as well as the limitation of in vitro models in answering these questions. Human & Experimental Toxicology (2007) 26, 295-302

Key Words: in vitro cell culture • manganese • metal transporters • rat brain endothelial cells (RBE4)


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