Metabolic rate of membrane-permeant diacylglycerol and its relation to human resting T-lymphocyte activation.
DL-1,2-Dioctanoylglycerol (1,2-DiC8) added to human peripheral resting T lymphocytes was rapidly metabolized to produce octanoic acid and further to small molecules, probably by the action of diacylglycerol lipase and/or nonspecific esterase. Only a small portion was converted to the corresponding phosphatidic acid or was isomerized to 1,3-DiC8 before being metabolized. The uptake of 1,2-DiC8 by the cell was apparently fast, and the rate of disappearance of 1,2-DiC8 was dependent on the cell densities; at a higher density of T lymphocytes 1,2-DiC8 was removed quickly, whereas at a lower cell density 1,2-DiC8 remained for a longer period of time. With a fixed amount of 1,2-DiC8 added, the extent of interleukin 2 receptor alpha-subunit (IL-2R alpha) expression was inversely related to the cell density and proportional to the duration of exposure of the cells to 1,2-DiC8. Repeated doses of 1,2-DiC8 potentiated IL-2R alpha expression. In contrast, a single dose of phorbol 12-myristate 13-acetate caused T-lymphocyte activation to similar extents irrespective of the cell density, probably because the phorbol ester was not metabolized and remained in membranes. The available evidence supports a proposal made in a previous paper and indicates that the sustained activation of protein kinase C for at least the first 3-4 hr is essential for the activation of resting T lymphocytes.
Asaoka
Y
Y
Biosignal Research Center, Kobe University, Japan.
Oka
M
M
Yoshida
K
K
Nishizuka
Y
Y
D001692:Biological Transport; D002463:Cell Membrane Permeability; D004075:Diglycerides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; C013965:diolein