Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/22/2002
Publication Date: 8/1/2002
Citation: BANKS, W.A., NIEHOFF, M.L., BROWN, R.L., CHEN, Z.Y., CLEVELAND, T.E. TRANSPORT ACROSS THE BLOOD-BRAIN BARRIER OF AN ANTIFUNGAL TRYPSIN INHIBITOR ISOLATED FROM CORN. JOURNAL OF BIOLOGICAL CHEMISTRY. 2002. V. 46(8). P. 2633-2635. Interpretive Summary: The fungus Aspergillus flavus infects agricultural commodities such as corn. A corn kernel protein that inhibits growth of Aspergillus flavus was previously discovered. Since Aspergillus flavus has been identified in the medical community as one of the primary fungi infecting the central nervous system of patients with compromised immune systems, the corn protein was tested for potential as an anti-infective agent for humans. After the cor protein was injected into mice, it was shown to cross the blood-brain barrier (BBB) of the mice and to enter the brain. Ability to cross the BBB is an important characteristic of a chemical compound being considered for pharmaceutical usage. This study suggests evaluations of the effectiveness of the corn protein in mammalian systems may be warranted. Favorable results could lead to the development of future products aimed at protecting patients whose immune systems have been compromised.
Technical Abstract: Fungal infections of the central nervous system (CNS) are difficult to treat because of the poor penetration of clinically available antifungal agents. We determined here whether a promising 14-kDa protein trypsin inhibitor (TI) isolated from a line of corn resistant to Aspergillus flavus could cross the blood-brain barrier (BBB) of the mouse. TI was radioactively labeled with **131I (I-TI) and injected intravenously. I-TI crossed the BBB at a rate of 0.153 ul/g-min with about 0.082 percent of the iv injected dose taken up per g of brain. HPLC and acid precipitation showed that radioactivity recovered from brain and arterial serum represented intact I-TI. Capillary depletion showed that I-TI was completely transported across the BBB and entered the parenchyma of the brain. Transport of I-TI was saturable with 58 ng/mouse of unlabeled TI inhibiting transport by 50 percent. These results suggest that TI has the potential to be effective after iv administration in treating CNS fungal infections.