Biochemical mechanisms of calcium mobilisation induced by mastoparan and chimeric hormonewmastoparan constructs

Longland, Clare L.; Mezna, Mokdad; Langel, Ülo; Hällbrink, Mattias; Soomets, Ursel; Wheatley, Mark; Michelangeli, Francesco; Howl, John

doi:10.1016/s0143-4160(98)90086-0

Cited by 36 publications

(38 citation statements)

References 26 publications

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“…21. D, the thapsigargin inhibition of Ca 2+ ATPase activity using membranes derived from skeletal muscle SR ( ▪ ) and brain microsomes ( • ).…”

Section: Discussionmentioning

confidence: 99%

“…E, the effects of alisol A ( • ) and alisol B ( ▪ ) on the Ca 2+ ATPase activity measured in brain microsomes as described in ref. 21. Points, mean of 3 to 5 replicates; bars, SEM.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the relatively low level of Ca 2+ ATPase activity in these microsomal membranes, the rate of Ca 2+ -dependent ATP hydrolysis were measured using the more sensitive phosphate liberation assay, described in ref. (21). All SERCA inhibition data were fitted to the allostearic dose versus effect equation using Fig P (Biosoft):…”

Section: The Measurement Of Serca Activitymentioning

confidence: 99%

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Alisol B, a Novel Inhibitor of the Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase Pump, Induces Autophagy, Endoplasmic Reticulum Stress, and Apoptosis

Law

Wang

et al. 2010

Molecular Cancer Therapeutics

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Emerging evidence suggests that autophagic modulators have therapeutic potential. This study aims to identify novel autophagic inducers from traditional Chinese medicinal herbs as potential antitumor agents. Using an image-based screen and bioactivity-guided purification, we identified alisol B 23-acetate, alisol A 24-acetate, and alisol B from the rhizome of Alisma orientale as novel inducers of autophagy, with alisol B being the most potent natural product. Across several cancer cell lines, we showed that alisol B-treated cells displayed an increase of autophagic flux and formation of autophagosomes, leading to cell cycle arrest at the G 1 phase and cell death. Alisol B induced calcium mobilization from internal stores, leading to autophagy through the activation of the CaMKK-AMPK-mammalian target of rapamycin pathway. Moreover, the disruption of calcium homeostasis induces endoplasmic reticulum stress and unfolded protein responses in alisol B-treated cells, leading to apoptotic cell death. Finally, by computational virtual docking analysis and biochemical assays, we showed that the molecular target of alisol B is the sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase. This study provides detailed insights into the cytotoxic mechanism of a novel antitumor compound. Mol Cancer Ther; 9(3); 718-30. ©2010 AACR.

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“…21. D, the thapsigargin inhibition of Ca 2+ ATPase activity using membranes derived from skeletal muscle SR ( ▪ ) and brain microsomes ( • ).…”

Section: Discussionmentioning

confidence: 99%

“…E, the effects of alisol A ( • ) and alisol B ( ▪ ) on the Ca 2+ ATPase activity measured in brain microsomes as described in ref. 21. Points, mean of 3 to 5 replicates; bars, SEM.…”

Section: Discussionmentioning

confidence: 99%

Section: The Measurement Of Serca Activitymentioning

confidence: 99%

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Alisol B, a Novel Inhibitor of the Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase Pump, Induces Autophagy, Endoplasmic Reticulum Stress, and Apoptosis

Law

Wang

et al. 2010

Molecular Cancer Therapeutics

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120

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“…In a previous study (13), we showed that mastoparan and a number of closely related analogues inhibit the SR Ca 2ϩ -ATPase. Here we elucidate the mechanism of this inhibition.…”

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confidence: 95%

“…Mastoparan (MP) is an amphiphilic tetradecapeptide isolated from wasp venom (11). It is known to possess a variety of biological activities including mast cell degranulation, mobilization of Ca 2ϩ from cerebellar microsomes and sarcoplasmic reticulum, activation of the ryanodine receptor and modulation of various enzymes, for example the Na ϩ /K ϩ -ATPase of rat brain (12)(13)(14).…”

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confidence: 99%

The Mechanism of Inhibition of the Ca2+-ATPase by Mastoparan

Longland

Mezna

Michelangeli

1999

Journal of Biological Chemistry

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Inhibition of the sarcoplasmic/endoplasmic reticulum Ca²⁺‐ATPase by flavonoids: A quantitative structure‐activity relationship study

et al. 2008

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SummaryFlavonoids are commonly found in fruit and vegetables and have been shown to reach concentrations of several micromolars in human blood plasma. Flavonoids are also believed to have cancer chemoprotective properties. One hypothesis is that flavonoids are able to initiate apoptosis, especially in cancer cells, via a Ca 21 -dependent mitochondrial pathway. This pathway can be activated through an exaggerated elevation of cytosolic [Ca 21 ], and sarcoplasmic/endoplasmic reticulum Ca 21 -ATPases (SERCA) play an essential role in ameliorating such changes. In this study, we demonstrate that flavonoids (especially flavones) can inhibit the activity of Ca 21 -ATPases isoforms SERCA1A and SERCA2B in the micromolar concentration range. Of the 25 flavonoids tested, 3,6-dihydroxyflavone (IC 50 , 4.6 lM) and 3,3 0 ,4 0 ,5,7-pentahydroxyflavone (quercetin) (IC 50 , 8.9 lM) were the most potent inhibitors. We show that polyhydroxylation of the flavones are important for inhibition, with hydroxylation at position 3 (for SERCA1A) and position 6 (for SERCA2B) being particularly relevant.2008 IUBMB IUBMB Life, 60(12): 853-858, 2008

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Biochemical mechanisms of calcium mobilisation induced by mastoparan and chimeric hormonewmastoparan constructs

Cited by 36 publications

References 26 publications

Alisol B, a Novel Inhibitor of the Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase Pump, Induces Autophagy, Endoplasmic Reticulum Stress, and Apoptosis

Alisol B, a Novel Inhibitor of the Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase Pump, Induces Autophagy, Endoplasmic Reticulum Stress, and Apoptosis

The Mechanism of Inhibition of the Ca2+-ATPase by Mastoparan

Inhibition of the sarcoplasmic/endoplasmic reticulum Ca²⁺‐ATPase by flavonoids: A quantitative structure‐activity relationship study

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Biochemical mechanisms of calcium mobilisation induced by mastoparan and chimeric hormonewmastoparan constructs

Cited by 36 publications

References 26 publications

Alisol B, a Novel Inhibitor of the Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase Pump, Induces Autophagy, Endoplasmic Reticulum Stress, and Apoptosis

Alisol B, a Novel Inhibitor of the Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase Pump, Induces Autophagy, Endoplasmic Reticulum Stress, and Apoptosis

The Mechanism of Inhibition of the Ca2+-ATPase by Mastoparan

Inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase by flavonoids: A quantitative structure‐activity relationship study

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Inhibition of the sarcoplasmic/endoplasmic reticulum Ca²⁺‐ATPase by flavonoids: A quantitative structure‐activity relationship study