Regulation of tissue transglutaminase by prolonged increase of intracellular Ca2+, but not by initial peak of transient Ca2+ increase.
Tissue transglutaminase (tTGase) is a member of calcium-dependent transamidation enzyme family, but a detailed regulation mechanism of tTGase by intracellular Ca(2+) is not clearly understood. Arachidonic acid (AA) and maitotoxin (MTX) activated tTGase in a dose- and time-dependent manner. Transfection of tTGase siRNA largely inhibited tTGase expression and tTGase activation by MTX. AA induced an initial increase of intracellular Ca(2+) followed by a prolonged increase. Removal of extracellular Ca(2+) with EGTA blocked the prolonged Ca(2+) increase in response to AA, although the initial Ca(2+) increase remained. In contrast, EGTA completely blocked the increase of intracellular Ca(2+) by MTX. The activation of tTGase by AA or MTX was significantly inhibited by EGTA. Moreover, EGTA prevented the prolonged increase of intracellular Ca(2+) and tTGase activation by lysophosphatidic acid, but had no effect on the initial Ca(2+) increase. These results suggested that tTGase is regulated by the prolonged increase of intracellular Ca(2+) originated from Ca(2+) influx, rather than by the initial peak of transient Ca(2+) increase.
Yoo
Je-Ok
JO
Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine, Chunchon, Republic of Korea.
Yi
Sun-Ju
SJ
Choi
Hyun Jung
HJ
Kim
Woo Jin
WJ
Kim
Young-Myeong
YM
Han
Jeong-A
JA
Ha
Kwon-Soo
KS
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology; D008387:Marine Toxins / Q000494:pharmacology; D051379:Mice; D035964:Oxocins / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D011503:Transglutaminases / Q000378:metabolism*; D000095702:Polyether Toxins
D016718:Arachidonic Acid; D002118:Calcium; D002413:Cations, Divalent; D004533:Egtazic Acid; D008246:Lysophospholipids; D008387:Marine Toxins; D035964:Oxocins; D034741:RNA, Small Interfering; D011503:Transglutaminases; C020394:maitotoxin; D000095702:Polyether Toxins; C032881:lysophosphatidic acid