Hs. Minhas et Pj. Thornalley, COMPARISON OF THE DELIVERY OF REDUCED GLUTATHIONE INTO P388D(1) CELLSBY REDUCED GLUTATHIONE AND ITS MONOETHYL AND DIETHYL ESTER DERIVATIVES, Biochemical pharmacology, 49(10), 1995, pp. 1475-1482
The effect of reduced glutathione, reduced glutathione monoethyl eater
and reduced glutathione diethyl ester on the cellular concentration o
f reduced glutathione and cysteine in P388D(1) macrophages in vitro, a
nd the cellular and extracellular de-esterification of reduced glutath
ione esters, was investigated. At 1 mM reduced glutathione derivative,
only reduced glutathione diester markedly increased the cellular conc
entration of reduced glutathione. There was little delivery of reduced
glutathione monoethyl ester into the cells. Reduced glutathione, and
monoethyl and diethyl ester derivatives all increased the cellular con
centration of cysteine; reduced glutathione diethyl ester also increas
ed the cellular concentration of gamma-glutamylcysteine. Reduced gluta
thione esters were de-esterified intracellularly where the diester was
rapidly converted to the monoester. The diester was also converted to
the monoester extracellularly by interaction with cell surface estera
ses and by a much slower spontaneous hydrolysis. This indicates that t
he diester of reduced glutathione was a much more effective vehicle fo
r delivery of reduced glutathione into cells than the monoester. Reduc
ed glutathione diester also increased the cellular concentrations of c
ysteine and gamma-glutamylcysteine, suggesting that de novo synthesis
of reduced glutathione was also stimulated.