42002:

Thioredoxin: A Photosynthetic Regulatory Protein Mitigating Food Allergies.

Authors:	Buchanan, Bob, B.(A)del Val, Gregorio(A)Frick, Oscar, L.(B)
Affiliations:	(A): University of California, Berkeley (B): University of California, San Francisco
Presenter:	Buchanan, Bob B., view@nature.berkeley.edu

For the past three decades, the laboratory of one of us (BBB) has worked on thioredoxin, a ubiquitous 12kDa regulatory protein with a catalytically active disulfide group. Following the description and elucidation of a number of functions of the oxygenic photosynthetic system--named the ferredoxin/thioredoxin system--attention was turned to the NADP/thioredoxin system that also occurs in plants (Eq. 1). 1. NADPH + H+ + Thioredoxin hox –NTR -> NADP+ + Thioredoxin hred Thioredoxin h was identified as a participant of the system, which was found to be extraplastidic—i.e., occurring in the cytosol, mitochondrion and endoplasmic reticulum. Others subsequently showed thioredoxin h to be a member of a multigene family expressed throughout the plant. Ongoing work in Berkeley on cereals has shown thioredoxin h to act as an early signal in germination, reducing critical intramolecular disulfide bonds of target storage proteins, enzymes and enzyme inhibitor proteins, thereby facilitating the mobilization of nitrogen and carbon in the endosperm. The work on seeds opened the door to the potential application of thioredoxin in improving foods in ways ranging from strengthening poor quality doughs to enhancing digestibility to mitigating allergies. We have studied the allergy application by using a colony of high IgE-producing dogs (established in 1980 by OLF), which appear to be an excellent model for humans. We have shown that thioredoxin, reduced by NADPH via NADP-thioredoxin reductase, in turn, reduces critical disulfide proteins of wheat, soy and milk and thereby mitigates their allergenic effects (Eq. 2). 2. Allergenox + Thioredoxinred -> Allergenred + Thioredoxinox Recently we obtained similar results for ragweed pollen. The ability of thioredoxin to mitigate each of these allergies rests on its unique ability to reduce the intramolecular disulfide bonds of responsible target proteins and thereby (1) change epitope accessibility so as to decrease recognition by the IgE immune system, and (2) increase susceptibility to proteases so as to allow digestion by pepsin in the stomach. We are actively pursing the application of thioredoxin to produce hypoallergenic, hyperdigestible foods and to improve allergy immunotherapy--i.e., the effectiveness and safety of the desensitization procedure.