The effects of cytochalasins on lymphocytes. Identification of distinct cytochalasin-binding sites in relation to mitogenic response and hexose transport.

Mookerjee, Basab K.; Cuppoletti, John; Rampal, Amrit L.; Jung, Chan Y.

doi:10.1016/s0021-9258(19)69962-x

Cited by 55 publications

(23 citation statements)

References 29 publications

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“…Analysis of the 1D NMR data for 1 revealed one carbonyl, three quaternary carbons, 15 methines, three methylenes, and three methyls. Comparison of the 1 H and 13 C NMR data of 1 with those of cytochalasin Z 7 showed the presence of the same 10-phenylsubstituted perhydroisoindol-1-one skeleton. Compound 1 differed from cytochalasin Z 7 only in the macrocyclic ring, where the R,βunsaturated ester system [C-19 (157.7, CH), C-20 (123.3, CH), C-21 (167.7, qC)] that is present in the 13 C NMR spectrum of cytochalasin Z 7 was missing, and chemical shifts of C-9 (δ C 79.4 qC) and C-18 (δ C 68.8 CH) in 1 were upfield and downfield, respectively, which suggested that two hydroxyl groups were located on C-9 and C-18 and the 12-membered macrocyclic ring in cytochalasin Z 7 was changed to an open chain in 1, which was consistent with the molecular formula.…”

Section: Resultsmentioning

confidence: 87%

“…Comparison of the 1 H and 13 C NMR data of 1 with those of cytochalasin Z 7 showed the presence of the same 10-phenylsubstituted perhydroisoindol-1-one skeleton. Compound 1 differed from cytochalasin Z 7 only in the macrocyclic ring, where the R,βunsaturated ester system [C-19 (157.7, CH), C-20 (123.3, CH), C-21 (167.7, qC)] that is present in the 13 C NMR spectrum of cytochalasin Z 7 was missing, and chemical shifts of C-9 (δ C 79.4 qC) and C-18 (δ C 68.8 CH) in 1 were upfield and downfield, respectively, which suggested that two hydroxyl groups were located on C-9 and C-18 and the 12-membered macrocyclic ring in cytochalasin Z 7 was changed to an open chain in 1, which was consistent with the molecular formula. The positions of the substituents in the open chain were confirmed as occurring at C-16 (methyl) and C-17 and C-18 (two hydroxyls) using the HMBC spectrum, which showed correlations from CH 3 -19 (1.19 ppm, d) to the two oxygenated methine sp 3 carbons C-17 (78.4 ppm, CH) and C-18 (68.8 ppm, CH) and correlations from CH 3 -20 (0.86 ppm, d) to C-15 (38.5 ppm, CH 2 ), C-16 (35.1 ppm, CH), and C-17.…”

Section: Resultsmentioning

confidence: 87%

“…Analysis of the 1D NMR spectra of 2 indicated that it had a structure very similar to 1. The only difference was that the 13 C NMR spectrum (Table 1) of 2 contained one more carbonyl carbon at 216.8 ppm (C-17, qC) in place of an oxygenated carbon at 78.4 ppm (C-17, CH) in 1. This change could be further confirmed by the HMBC correlations from CH 3 -19 (1.21 ppm, d) and CH 3 -20 (1.01 ppm, d) to the carbonyl carbon at 216.8 ppm (C-17, qC).…”

Section: Resultsmentioning

confidence: 99%

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Novel Open-Chain Cytochalsins from the Marine-Derived Fungus Spicaria elegans

et al. 2008

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Six novel open-chain cytochalasins (1-6) and one known [12]-cytochalasin (7) have been isolated from the fermentation broth of a marine-derived fungus, Spicaria elegans. Cytochalasins Z10-Z15 (1-6) are the first reported cytochalasins that contain an open chain to date. The structures of these new compounds were elucidated by spectroscopic methods. The cytotoxic effects on P388, A-549, HL-60, and BEL-7402 cell lines of all compounds were evaluated by the MTT method.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

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Novel Open-Chain Cytochalsins from the Marine-Derived Fungus Spicaria elegans

et al. 2008

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“…Given that the intensity of red fluorescent signal is proportional to the volume of intracellular acidic compartments, measurement of the mean red:green fluorescence ratio allows for characterization of the fractional volume of acidic vesicular compartments within a population of cells. , Acridine orange (ThermoFisher Inc.) was added to culture wells at a final concentration of 0.5 μg/mL for a period of 20 min at 37 °C. For pertinent experiments, Cytochalasin B (CB) (Sigma Aldrich) was dissolved in DMSO and added directly to culture media at a final concentration of 2 μM . Cells were then washed and fixed in 1% PFA in preparation for flow cytometry.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…For pertinent experiments, Cytochalasin B (CB) (Sigma Aldrich) was dissolved in DMSO and added directly to culture media at a final concentration of 2 μM. 32 Cells were then washed and fixed in 1% PFA in preparation for flow cytometry.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Direct Comparison of B Cell Surface Receptors as Therapeutic Targets for Nanoparticle Delivery of BTK Inhibitors

et al. 2021

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Targeting different cell surface receptors with nanoparticle (NP)-based platforms can result in differential particle binding properties that may impact their localization, bioavailability, and, ultimately, the therapeutic efficacy of an encapsulated payload. Conventional in vitro assays comparing the efficacy of targeted NPs often do not adequately control for these differences in particle–receptor binding, potentially confounding their therapeutic readouts and possibly even limiting their experimental value. In this work, we characterize the conditions under which NPs loaded with Bruton’s Tyrosine Kinase (BTK) inhibitor differentially suppress primary B cell activation when targeting either CD19 (internalizing) or B220 (noninternalizing) surface receptors. Surface binding of fluorescently labeled CD19- and B220-targeted NPs was analyzed and quantitatively correlated with the number of bound particles at given treatment concentrations. Using this binding data, suppression of B cell activation was directly compared for differentially targeted (CD19 vs B220) NPs loaded with a BTK inhibitor at a range of particle drug loading concentrations. When NPs were loaded with lower amounts of drug, CD19-mediated internalization demonstrated increased inhibition of B cell proliferation compared with B220 NPs. However, these differences were mitigated when particles were loaded with higher concentrations of BTK inhibitor and B220-mediated “paracrine-like” delivery demonstrated superior suppression of cellular activation when cells were bound to lower overall numbers of NPs. Taken together, these results demonstrate that inhibition of B cell activation can be optimized for NPs targeting either internalizing or noninternalizing surface receptors and that particle internalization is likely not a requisite endpoint when designing particles for delivery of BTK inhibitor to B cells.

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Interaction of AU-rich sequence binding proteins with actin: Possible involvement of the actin cytoskeleton in lymphokine mRNA turnover

1997

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In the current study, we report that cytochalasin-induced disruption of microfilaments stabilizes lymphokine mRNAs in activated human peripheral blood lymphocytes. Parallel with this, a dose-and time-dependent increase in AU-rich sequence binding protein (AUPB) activities is apparent in the nonionic detergentresistant fractions of these cells, suggesting that cytochalasin-induced modulation of lymphokine mRNA stability might be mediated through cytoplasmic AUBPs. We provide evidence that some of the AUBPs can be immunoprecipitated with anti-actin antibodies, implicating the potential of these proteins to associate with the actin-based cytoskeleton in vivo. Moreover, disruption of the microfilament network by cytochalasins produces increased immunoprecipitable actin-AUBP complexes in the detergent-resistant cytoplasmic subfractions of lymphocytes. We show that cytochalasin-induced changes in AUBP activities are parallel with their higher binding affinity to RNA containing AU-rich instability sequence element as judged by in vitro competition and in vivo ultraviolet-crosslinking analysis. Correlation of these findings with changes in mRNA stability indicates that the actin cytoskeleton may play a physiologically important role in posttranscriptional regulation of lymphokine gene expression during early lymphocyte activation.

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The effects of cytochalasins on lymphocytes. Identification of distinct cytochalasin-binding sites in relation to mitogenic response and hexose transport.

Cited by 55 publications

References 29 publications

Novel Open-Chain Cytochalsins from the Marine-Derived Fungus Spicaria elegans

Novel Open-Chain Cytochalsins from the Marine-Derived Fungus Spicaria elegans

Direct Comparison of B Cell Surface Receptors as Therapeutic Targets for Nanoparticle Delivery of BTK Inhibitors

Interaction of AU-rich sequence binding proteins with actin: Possible involvement of the actin cytoskeleton in lymphokine mRNA turnover

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