Effects of selenium compounds on phospholipid/Ca2+-dependent protein kinase (protein kinase C) system from human leukemic cells.
Selenium compounds (selenium dioxide, selenious acid, and selenic acid) were found to inhibit phospholipid/Ca2+-dependent protein kinase (protein kinase C) and the phorbol ester-stimulated phosphorylation of endogenous substrate proteins from HL60 cells. Kinetic analysis indicated that selenium dioxide (SeO2) inhibited the enzyme noncompetitively with respect to phosphatidylserine (apparent Ki, 60 microM) and Ca2+ (apparent Ki, 68 microM). The inhibitory effect of SeO2 on protein kinase C was additive to that of another inhibitor of the enzyme (alkyl-lysophospholipid) when present together. SeO2 was also equally inhibitory to myosin light chain kinase, a calmodulin/Ca2+-dependent class of protein kinase. It, however, affected only very slightly cyclic adenosine 3':5'-monophosphate-dependent protein kinase. It is suggested that inhibition of Ca2+-dependent reactions might be related to the anticarcinogenic property of selenium.
Su
H D
HD
Shoji
M
M
Mazzei
G J
GJ
Vogler
W R
WR
Kuo
J F
JF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology*; D008246:Lysophospholipids; D009206:Myocardium / Q000201:enzymology; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D013552:Swine; D013629:Tamoxifen / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D008246:Lysophospholipids; D010718:Phosphatidylserines; D010743:Phospholipids; D013629:Tamoxifen; D011493:Protein Kinase C; D012643:Selenium; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium