Drug action of thapsigargin on the Ca2+ pump protein of sarcoplasmic reticulum.

Kijima, Yoshiyuki; Ogunbunmi, Eunice M.; Fleischer, Sidney

doi:10.1016/s0021-9258(18)54441-0

Cited by 156 publications

(17 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BHQ has been shown to reduce the affinity of the ATPase for Ca2+, due to a shift in the El-E2 equilibrium toward the E2 conformation (Wictome et al, 1992b). These effects of BHQ are very similar to those observed for thapsigargin and other sesquiterpene lactone inhibitors of the Ca2+-ATPase (Thastrup et al, 1990;Sagara & Inesi, 1991;Kijima et al, 1991;Lytton et al, 1991;Wictome et al, 1992aWictome et al, , 1995. As also observed with thapsigargin, BHQ reduces phosphorylation of the ATPase by P, (Wictome et al, 1992b), which is unexpected since in the El-E2 model for the ATPase it is the E2 conformation which is phosphorylated by P, (de Meis, 1981).…”

Section: Resultsmentioning

confidence: 71%

“…The Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum (SR)* 1 is inhibited by two classes of hydrophobic molecule, the sesquiterpene lactones including thapsigargin, thapsivillosin A (TvA), and trilobolide (Thastrup et al, 1990;Sagara & Inesi, 1991; Kijima et al, 1991;Lytton et al, 1991;Wictome et al, 1992aWictome et al, , 1995, and the dihydroxybenzenes (or hydroquinones) including 2,5-di-terí-butyl-1,4-dihydroxybenzene (BHQ) (Llopis et al, 1991;Wictome et al, 1992bWictome et al, , 1994Nakamura et al, 1992). Both the sesquiterpene lactones and BHQ have been shown to shift the E1/E2 equilibrium of the ATPase toward E2 with a decrease in the rate of the E2 -* El transition, explaining the inhibition of ATPase activity by these compounds (Wictome et al, 1992b).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interactions of Dihydroxybenzenes with the Ca2+-ATPase: Separate Binding Sites for Dihydroxybenzenes and Sesquiterpene Lactones

Ym¹,

Wictome²,

Jm³

et al. 1995

Biochemistry

View full text Add to dashboard Cite

The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum is inhibited by 2,5-di-tert-butyl-1,4-dihydroxybenzene (BHQ) and other hydrophobic 1,4-dihydroxybenzenes. Inhibitory potency increases on increasing substituent chain length from 2,5-dipropyl-1,4-dihydroxybenzene to 2,5-di-tert-amyl-1,4-dihydroxybenzene, the most potent inhibitor, but then decreases for 2,5-bis(7-methylheptyl)-1,4-dihydroxybenzene. Kinetic measurements are consistent with isomerization following the initial binding of BHQ to the ATPase to give a modified E2 conformation, E2AI, as for the binding of sesquiterpene lactones, such as thapsigargin. Binding of BHQ to the ATPase shifts the E1-E2 equilibrium toward E2 because of the formation of E2AI. Measurements of Ca2+ binding as a function of BHQ concentration suggest that BHQ can bind to the E1 conformation of the ATPase (but without the subsequent conformational change observed on binding to E2) and that the binding constants of E1 for Ca2+ are unaffected by binding of BHQ. Binding of BHQ to the ATPase in the presence of substoichiometric amounts of thapsivillosin A and effects of mixtures of BHQ and thapsivillosin A show that these two inhibitors have separate binding sites on the ATPase.

show abstract

Section: Resultsmentioning

confidence: 71%

mentioning

confidence: 99%

Interactions of Dihydroxybenzenes with the Ca2+-ATPase: Separate Binding Sites for Dihydroxybenzenes and Sesquiterpene Lactones

Ym¹,

Wictome²,

Jm³

et al. 1995

Biochemistry

View full text Add to dashboard Cite

show abstract

“…This result makes it very unlikely that inhibition of export from the ER by mastoparan is related to direct or indirect effects on the phosphatase/kinase cascade regulating ER export during mitosis (Davidson et al, 1992). In addition, given the potential for mastoparan to activate G protein-regulated calcium channels (Lotersztajn et al, 1992), we have examined the effect of thapsigargan (Thastrop, 1990;Lytton et al, 1991;Ghosh et al, 1991;Kijima et al, 1991), a potent inhibitor of ER calcium channels leading to a rapid elevation of intracellular calcium, on VSV-G export. We found no effect of the drug at concentrations as high as 2.5 #M in vitro (Balch, W. E., and H. Plutner, unpublished observations).…”

Section: Role Of Heterotrimeric G Proteins In Transport: Effect Of Mastoparanmentioning

confidence: 99%

Multiple GTP-binding proteins regulate vesicular transport from the ER to Golgi membranes.

Schwaninger

Plutner

Bokoch

et al. 1992

The Journal of Cell Biology

118

View full text Add to dashboard Cite

show abstract

“…A number of inhibitors of the Ca2+-ATPase of sarcoplasmic reticulum (SR)1 are known, including the sesquiterpene lactones thapsigargin (Bruñe & Ullrich, 1991;Sagara & Inesi, 1991;Kijima et al, 1991;Lytton et al, 1991;Wictome et al, 1992a,b;Sagara et al, 1992) trilobolide, and thapsivillosin A (Henderson et al, 1994b); nonylphenol (Michelangeli et al, 1990b); and the hydroquinone 2,5-di-rerí-butyl-1,4-benzohydroquinone (Llopis et al, 1991;Wictome et al, 1992b;Lytton et al, 1991). Less is known, however, about molecules stimulating ATPase activity.…”

mentioning

confidence: 99%

Mechanism of Stimulation of the Calcium Adenosinetriphosphatase by Jasmone

Starling¹,

Hughes²,

East³

et al. 1994

Biochemistry

View full text Add to dashboard Cite

The ATPase activity of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum is increased ca. 3-fold at 25 degrees C and pH 7.2 by jasmone at a concentration of 100 microM, concentrations above 10 mM resulting in reduced stimulation. Stimulation by methyl jasmonate, menthol, or menthone requires much higher concentrations. Effects of jasmone are much less marked at 37 degrees C than at 25 degrees C, and much higher concentrations of jasmone are required to stimulate ATPase activity at pH 6.0 than at pH 7.2. The effects of jasmone on the ATPase are highly specific. Jasmone has no effect on the E1<-->E2 equilibrium constant for the ATPase or on Ca2+ binding. The rate of phosphorylation by ATP is unaffected by jasmone, and only small effects are seen on the reaction of the phosphorylated ATPase with ADP. Jasmone does, however, increase the rate of dephosphorylation by a factor of 2 and the rate of dissociation of Ca2+ from the phosphorylated ATPase by a factor of 3. Jasmone decreases the level of phosphorylation of the ATPase by P(i) in the absence of Ca2+ consistent with a decrease in the equilibrium constant E2P(i)Mg<-->E2PMg. Reconstitution of the ATPase with dimyristoleoylphosphatidylcholine decreases the stoichiometry of Ca2+ binding from the usual 2:1 to 1:1. Unlike other hydrophobic molecules, jasmone failed to reverse this effect. Further, jasmone had very similar effects on the activity of the ATPase reconstituted with either dimyristoleoylphosphatidylcholine or dioleoylphosphatidylcholine, whereas other hydrophobic molecules caused a much greater stimulation of activity for the ATPase reconstituted with the short-chain lipid.

show abstract

Drug action of thapsigargin on the Ca2+ pump protein of sarcoplasmic reticulum.

Cited by 156 publications

References 32 publications

Interactions of Dihydroxybenzenes with the Ca2+-ATPase: Separate Binding Sites for Dihydroxybenzenes and Sesquiterpene Lactones

Interactions of Dihydroxybenzenes with the Ca2+-ATPase: Separate Binding Sites for Dihydroxybenzenes and Sesquiterpene Lactones

Multiple GTP-binding proteins regulate vesicular transport from the ER to Golgi membranes.

Mechanism of Stimulation of the Calcium Adenosinetriphosphatase by Jasmone

Contact Info

Product

Resources

About