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Tissue‐distribution of claudin‐3/‐4 binder, the C‐terminal fragment of Clostridium perfringens enterotoxin, in mice
Author(s) -
Li Xiangru,
Kondoh Masuo,
Watari Akihiro,
Yagi Kiyohito
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.895.4
Subject(s) - enterotoxin , kidney , mutant , clostridium perfringens , microbiology and biotechnology , thyroid , toxin , chemistry , biology , pharmacology , endocrinology , biochemistry , gene , escherichia coli , bacteria , genetics
The C‐terminal fragment of Clostridium perfringens enterotoxin (C‐CPE) is the most well‐characterized claudin‐3 and ‐4 (CL‐3 and ‐4) binder. The mucosal absorption‐enhancing activity of C‐CPE is over 400‐fold more potent than a clinically used enhancer. C‐CPE has potential in cancer therapy and for mucosal vaccination. Since CL‐3 and ‐4 are ubiquitously expressed in heart, lung, liver, kidney, thyroid gland, stomach, and intestine, safety evaluations are important for their future therapeutic use. Here, we investigated the tissue distribution of C‐CPE in mice after intravenous administration. We prepared CF750‐labeled wild‐type C‐CPE and C‐CPE harboring mutant CL‐3/‐4 binding regions. FACS analysis showed that labeled wild‐type C‐CPE bound to CL‐4 but that labeled mutant C‐CPE did not, indicating that labeling did not alter the CL‐binding properties of C‐CPE. Most wild‐type and mutant C‐CPE promptly accumulated in the kidney, and C‐CPE were more distributed in the liver, thyroid gland and intestine than mutant C‐CPE 10 min after administration. The distribution of C‐CPE gradually decreased in the liver, thyroid gland and intestine, but the distribution of C‐CPE increased in the kidney until 48 h after administration. These findings suggest that the influence of CL‐3/‐4 binders on the liver, thyroid gland, intestine and kidney should be considered for future therapeutic applications.