Thapsigargin Facts Sheet (main)

This mini website about thapsigargin was prepared by a student of BioInformatics, the Open University.

alternate names: thapsigargin

 

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Thapsigargin, a plant-derived sesquiterpene lactone (see above), is an extremely tight-binding inhibitor of intracellular calcium (SERCA) pumps. We have shown that, in contrast to its well known inhibition of the catalytic cycle as a whole, thapsigargin binding actually activates phosphate-HOH oxygen exchange by enhancing the hydrolysis of the E2P (see catalytic cycle). Thapsigargin greatly stabilises the pump against denaturation in detergent, which suggests that it locks the membrane helices together. This in turn suggests that the oxygen exchange and accompanying domain movements in the head region of the protein are not linked to full counter transport of protons, as previously hypothesised, but rather may be associated with a single protonated form of the pump.\

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Prostate cancer specific derivatives of thapsigargin ... Although blocking SOCs offers one approach to depleting intracellular calcium, this end-point can also be achieved through the use of thapsigargin and its derivatives which target intracellular stores directly to induce apoptosis in prostate cancer cells. Thapsigargin is not however selective to the prostate and to avoid the risk of side-effects, Danish researchers in collaboration with Johns Hopkins Oncology Center have developed a series of inactive Thapsigargin prodrugs that can be activated by PSA. The prodrugs thus synthesized demonstrated prostate cancer specificity suggesting that they may represent novel therapeutic candidates for this disease.. ..

Where to buy:

AGscientific: 10 mg = $290

LClabs: 10 mg = $245

the 10 selected thapsigargin abstracts

1	Effects of ionomycin and thapsigargin on ion currents in oocytes of Bufo arenarum.
2	Biochemical characterization, distribution and phylogenetic analysis of Drosophila melanogaster ryanodine and IP3 receptors, and thapsigargin-sensitive Ca2+ ATPase.
3	Histamine potentiates IP(3)-mediated Ca(2+) release via thapsigargin-sensitive Ca(2+) pumps.
4	Bax plays a pivotal role in thapsigargin -induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo and Omi/HtrA2 release from mitochondria
5	The effects of nifedipine and thapsigargin on the responses of pressurized rat mesenteric artery to 5-hydroxytryptamine and norepinephrine.
6	The effect of ursodeoxycholic acid on the survivin in thapsigargin-induced apoptosis.
7	Role of protein tyrosine phosphorylation in the thapsigargin-induced intracellular Ca(2+) store depletion during human sperm acrosome reaction.
8	A gonadotropin-releasing hormone insensitive, thapsigargin-sensitive Ca2+ store reduces basal gonadotropin exocytosis and gene expression: comparison with agonist-sensitive Ca2+ stores.
9	Effects of thapsigargin on stimulation frequency--dependent changes in mitochondrial calcium in rat cardiac myocytes.
10	Thapsigargin blocks STP and LTP related calcium enhancements in hippocampal CA1 area.

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References:
1. Wong, W.E. et al. (1993) Biochem. 289, 71-9
2. Low, A.M. et al. (1993) Eur. J. Pharmacol. 230, 53-62
3. Charlesworth, A. & Rozengurt, E. (1994) J. Biol. Chem. 269, 32528-35
4. Foskett, J.K. & Wong, D.C. (1994) J. Biol. Chem. 269, 31525-32
5. Furuya, Y. et al. (1994) Cancer Res. 54, 6167-75
6. Palmer, F.P. et al. (1994) Biochim. Biophys. Acta 1215, 190-7

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