The structure-activity relationship of various YO compounds, novel plasmin inhibitors, in the apoptosis induction.
We have previously reported that YO-2, a selective plasmin inhibitor, induces thymocyte apoptosis. To elucidate the mechanism of YO-2-induced apoptosis, other YO compounds with different plasmin inhibitory action were tested for the pro-apoptotic activity in this study. The treatment of rat thymocytes with the YO compounds which had the hydrophobic but not the hydrophilic moiety at the C-terminal increased DNA fragmentation, the number of condensed nuclei and caspase-3-like activity. All pro-apoptotic YO compounds not only were potent plasmin inhibitors but also had the hydrophobic C-terminal as the common structure. Therefore, the target molecule of the YO compounds may be located not on the cell surface but rather inside the cells.
Enomoto
Riyo
R
Department of Pharmacology, Kobe Gakuin University, Ikawadani-cho, Nishi, Kobe 651-2180, Japan.
Sugahara
Chiyoko
C
Komai
Tomoe
T
Suzuki
Chie
C
Kinoshita
Noriko
N
Hosoda
Akiko
A
Yoshikawa
Asa
A
Tsuda
Yuko
Y
Okada
Yoshio
Y
Lee
Eibai
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D004151:Dipeptides; C419204:YO 1 compound; C419205:YO 2 compound; D005341:Fibrinolysin