Pressure tuning infrared spectroscopic study of cisplatin-induced structural changes in a phosphatidylserine model membrane

Taylor, Kmg; Goel, Rakesh; Shirazi, Farshad H.; Molepo, M.; Popovic, P.; Stewart, David J.; Wong, P. T. T.

doi:10.1038/bjc.1995.521

Cited by 18 publications

(12 citation statements)

References 33 publications

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“…First, in patients, cisplatin elicits a range of short-term secondary effects that include disturbance of the hydroelectrolytic balance, gastrointestinal troubles, hearing alterations, imbalance, and modified perceptions or sensations. Second, in cellular models, cisplatin acts on microtubules (4) and actin polymerization (5) and can modify or interact with phospholipids (6,7). Other studies including genetic screens for cisplatin resistance have documented that membrane proteins (8), enzymes involved in lipid synthesis and modification (9), or cellular enzymes (10) are affected by this drug.…”

Section: Introductionmentioning

confidence: 99%

Nongenomic Effects of Cisplatin: Acute Inhibition of Mechanosensitive Transporters and Channels without Actin Remodeling

et al. 2010

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Cisplatin is an antineoplastic drug, mostly documented to cause cell death through the formation of DNA adducts. In patients, it exhibits a range of short-term side effects that are unlikely to be related to its genomic action. As cisplatin has been shown to modify membrane properties in different cell systems, we investigated its effects on mechanosensitive ion transporters and channels. We show here that cisplatin is a noncompetitive inhibitor of the mechanosensitive Na + /H + exchanger NHE-1, with a half-inhibition concentration of 30 μg/mL associated with a decrease in V max and Hill coefficient. We also showed that it blocks the Cl − and K + mechanosensitive channels VSORC and TREK-1 at similar concentrations. In contrast, the nonmechanosensitive Cl − and K + channels CFTR and TASK-1 and the Na + -coupled glucose transport, which share functional features with VSORC, TREK-1, and NHE-1, respectively, were insensitive to cisplatin. We next investigated whether cisplatin action was due to a direct effect on membrane or to cortical actin remodeling that would affect mechanosensors. Using scanning electron microscopy, in vivo actin labeling, and atomic force microscopy, we did not observe any modification of the Young's modulus and actin cytoskeleton for up to 60 and 120 μg/mL cisplatin, whereas these concentrations modified membrane morphology. Our results reveal a novel mechanism for cisplatin, which affects mechanosensitive channels and transporters involved in cell fate programs and/or expressed in mechanosensitive organs in which cisplatin elicits strong secondary effects, such as the inner ear or the peripheral nervous system. These results might constitute a common denominator to previously unrelated effects of this drug.

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Section: Introductionmentioning

confidence: 99%

Nongenomic Effects of Cisplatin: Acute Inhibition of Mechanosensitive Transporters and Channels without Actin Remodeling

et al. 2010

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“…Many anticancer drugs show membrane effects via weak hydrophobic interaction or via electrostatic binding to membrane phospholipids before entering the cytoplasm. In this way, it has been shown that cisplatin can interact with phosphatidylserine to alter the characteristics of the membrane (10).…”

Section: Introductionmentioning

confidence: 99%

Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells

et al. 2007

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We have previously shown that cisplatin triggers an early acid sphingomyelinase (aSMase)-dependent ceramide generation concomitantly with an increase in membrane fluidity and induces apoptosis in HT29 cells. The present study further explores the role and origin of membrane fluidification in cisplatin-induced apoptosis. The rapid increase in membrane fluidity following cisplatin treatment was inhibited by membrane-stabilizing agents such as cholesterol or monosialoganglioside-1. In HT29 cells, these compounds prevented the early aggregation of Fas death receptor and of membrane lipid rafts on cell surface and significantly inhibited cisplatininduced apoptosis without altering drug intracellular uptake or cisplatin DNA adducts formation. Early after cisplatin treatment, Na + /H + membrane exchanger-1 (NHE1) was inhibited leading to intracellular acidification, aSMase was activated, and ceramide was detected at the cell membrane. Treatment of HT29 cells with Staphylococcus aureus sphingomyelinase increased membrane fluidity. Moreover, pretreatment with cariporide, a specific inhibitor of NHE1, inhibited cisplatin-induced intracellular acidification, aSMase activation, ceramide membrane generation, membrane fluidification, and apoptosis. Finally, NHE1-expressing PS120 cells were more sensitive to cisplatin than NHE1-deficient PS120 cells. Altogether, these findings suggest that the apoptotic pathway triggered by cisplatin involves a very early NHE1-dependent intracellular acidification leading to aSMase activation and increase in membrane fluidity. These events are independent of cisplatin-induced DNA adducts formation. The membrane exchanger NHE1 may be another potential target of cisplatin, increasing cell sensitivity to this compound. [Cancer Res 2007;67(16):7865-74]

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“…This spectral parameter has been used widely to monitor various structural and dynamic properties of a wide range of aqueous lipid bilayers and biomembranes. These structural and dynamic properties are: (i) large angle reorientational fluctuations (Auger, 1988;Tupper, 1992;; (ii) interchain packing (Siminovitch, 1987a;Wong, , 1984aWong, , 1989a; (iii) interchain and intrachain configuration distortion (Wong, 1985a); (iv) mechanism for the formation of the lamellar subgel phase (Wong, 1986); (v) interdigitation (Auger, 1988;Siminovitch, 1987bSiminovitch, , 1987cWong 1989b); (vi) interchain interactions (Hubner, 1990; Siminovitch, 1987b;Tupper, 1992); (vii) unsaturation induced changes in molecular configurations in lipid bilayers (Siminovitch, 1987a(Siminovitch, , 1987d; (viii) the effects of anesthetics (Auger, 1988(Auger, , 1990), toxins (Ahmed, 1992;, drugs (Popovic, 1992;Taylor, 1992), alkanes ), cholesterol (Wong, 1989a(Wong, , 1989c, polypeptides (Carrier, 1990), proteins (Gicquaud, 1992;Philp, 1990), fluorescent probes (Chong, 1989(Chong, , 1992, and other exogenous molecules (unpublished work from this laboratory) on the structural and dynamic properties in the bilayer interior of various lipids, and vice versa; (ix) the location and binding sites of these exogenous molecules in lipid bilayers (Ahmed, 1992;Auger, 1988Auger, , 1990Carrier, 1990;Chong, 1989Chong, , 1992; Gicquaud, 1992;Philp, 1990;…”

Section: Introductionmentioning

confidence: 99%

Pressure-induced correlation field splitting of vibrational modes: structural and dynamic properties in lipid bilayers and biomembranes

Wong

1994

Biophysical Journal

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Correlation field splittings of the vibrational modes of methylene chains in lipid bilayers, isolated lipid molecules in perdeuterated lipid bilayers, crystalline lipid, and interdigitated lipid bilayers have been investigated by pressure-tuning Fourier-transform infrared spectroscopy. The correlation field splittings of these modes are originating from the vibrational coupling interactions between the fully extended methylene chains with different site symmetry along each bilayer leaflet. The interchain-interactions of the methylene chains with the same site symmetry only contribute to frequency shift of the vibrational modes. The magnitude of the correlation field splitting is a measure of the strength of the interchain-interactions, and the relative intensities of the correlation field component bands provide information concerning the relative orientation of the zig-zag planes of the interacting methylene chains. It has been demonstrated in the present work that the correlation field splitting of the CH2 bending and rocking modes commonly observed in the vibrational spectra of lipid bilayers is the result of the intermolecular interchain-interactions among the methylene chains of the neighboring molecules. The intramolecular interchain-interactions between the sn-1 and sn-2 methylene chains within each molecule are weak. The correlation field splitting resulting from the intramolecular interchain-interactions exhibits a much smaller magnitude than that from the intermolecular interchain-interactions and is observed only at very high pressure. Interdigitation of the opposing bilayer leaflets disturbs significantly the intermolecular interchain-interactions and results in dramatic changes in the pressure profiles of the correlation field component bands of both the CH2 bending and rocking modes. The relative intensities of the correlation field component bands of these modes and the magnitude of the splitting are also altered significantly. These results provide further evidence that the correlation field splitting of the CH2 bending and rocking modes in the vibrational spectra of lipid bilayers is due to the intermolecular interchain-interactions. The present work has also demonstrated that the correlation field splitting of the vibrational modes in lipid bilayers is mainly contributed by the intermolecular interchain-interactions among the nearest neighboring molecules and that the long-range correlation interactions beyond the second neighboring molecules are insignificant.

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Pressure tuning infrared spectroscopic study of cisplatin-induced structural changes in a phosphatidylserine model membrane

Cited by 18 publications

References 33 publications

Nongenomic Effects of Cisplatin: Acute Inhibition of Mechanosensitive Transporters and Channels without Actin Remodeling

Nongenomic Effects of Cisplatin: Acute Inhibition of Mechanosensitive Transporters and Channels without Actin Remodeling

Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells

Pressure-induced correlation field splitting of vibrational modes: structural and dynamic properties in lipid bilayers and biomembranes

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