Actions of insulin-like growth factor binding protein-5 (IGFBP-5) are potentially regulated by tissue kallikrein in rat brains.
Tissue kallikrein (EC 3.4.21.35) that hydrolyzes kininogen and releases a physiologically active peptide, kinin, is found in rat brains. Insulin-like growth factor binding proteins (IGFBPs) that modulate IGF actions are also expressed in a variety of tissues including rat brains, and one of the major IGFBPs expressed in brain is known to be IGFBP-5, which is reported to be hydrolyzed in vitro by prostate-specific antigen (PSA) and gamma-nerve growth factor (gamma-NGF), both of which belong to the member of the kallikrein gene family. This study was designed to determine whether or not kallikrein has a potential to hydrolyze IGFBP-5 and their topographic proximity was investigated in rat brain using double immunohistochemical staining method. Immunohistochemically, IGFBP-5 positive cells were numerous and widespread in the cerebral cortex and belonged to neurons in the cell configuration. IGFBP-5 positive cells were negative for S-100 protein and were positive for betaIII tubulin, confirming them to be neurons. In addition, kallikrein positive cells were virtually all IGFBP-5 positive cells. IGFBP-5 was clearly hydrolyzed by kallikrein with cleavage sites of Arg188-Met189 and Arg136-Arg137 of IGFBP-5. Therefore, there is a possibility that kallikrein plays an important role in brain physiology, specifically in the neurons by regulating the actions of IGFBP-5 and IGF.
Iwadate
Hiromoto
H
Department of Materials Science and Engineering, Faculty of Science and Engineering, Tokyo University of Science, Yamaguchi, 1-1-1 Daigaku-Dori, Onoda, Yamaguchi 756-0884, Japan. iwa@ed.yama.tus.ac.jp
Sugisaki
Tetsuro
T
Kudo
Motoshige
M
Kizuki
Kazuyuki
K
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007124:Immunoenzyme Techniques; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism*; D007610:Kallikreins / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D013002:Somatomedins / Q000378:metabolism*
D018975:Insulin-Like Growth Factor Binding Protein 5; D013002:Somatomedins; D007610:Kallikreins