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PubMed2004

DNA damage tumor suppressor genes and genomic instability.

Disruption of the mechanisms that regulate cell-cycle checkpoints, DNA repair, and apoptosis results in genomic instability and the development of cancer in multicellular organisms. The protein kinases ATM and ATR, as well as their downstream substrates Chk1 and Chk2, are central players in checkpoint activation in response to DNA damage. Histone H2AX, ATRIP, as well as the BRCT-motif-containing molecules 53BP1, MDC1, and BRCA1 function as molecular adapters or mediators in the recruitment of ATM or ATR and their targets to sites of DNA damage. The increased chromosomal instability and tumor susceptibility apparent in mutant mice deficient in both p53 and either histone H2AX or proteins that contribute to the nonhomologous end-joining mechanism of DNA repair indicate that DNA damage checkpoints play a pivotal role in tumor suppression.

Animals↗
PubMed2006

The Acetic Acid Tolerance Response induces cross-protection to salt stress in Salmonella typhimurium.

Salmonella typhimurium induces an Acid Tolerance Response (ATR) upon exposure to mildly acidic conditions in order to protect itself against severe acid shock. This response can also induce cross-protection to other stresses such as heat and salt. We investigated whether both the acetic acid induced and lactic acid induced ATR in S. typhimurium provided cross-protection to a salt stress at 20 degrees C. Acid-adapted cells were challenged with both a sodium chloride (NaCl) and potassium chloride (KCl) shock and their ability to survive ascertained. Acetic acid adaptation provided cells with protection against both NaCl and KCl stress. However, lactic acid adaptation did not protect against either osmotic stressor and rendered cells hypersensitive to NaCl. These results have implications for the food industry where hurdle technology means multiple sub-lethal stresses such as mild pH and low salt are commonly used in the preservation of products.

Acetic Acid↗
PubMed2006

Effect of DC/mDC iontophoresis and terpenes on transdermal permeation of methotrexate: in vitro study.

The systemic toxicity caused by methotrexate limits its use and transdermal delivery would be a possible alternative. Transdermal permeation of methotrexate loaded into polyacrylamide-based hydrogel patch, across mice skin was studied in vitro after pretreatment with terpenes and ethanol, alone or in combination with iontophoresis (DC/mDC). Polyacrylamide patches gave the maximum flux as compared to the copolymers of acrylamide and acrylic acid. Of the terpenes used, pure menthol showed maximum enhancement (38%), whereas pure limonene elicited a minimum of 9.9% enhancement. Binary combination of menthol and ethanol increased the permeation to 54.9%, which was further enhanced to 93.69% and 117% when used in combination with DC and square wave (mDC) iontophoresis, respectively. ATR-FTIR of the stratum corneum treated with terpenes showed a split in the asymmetric C-H stretching vibrations along with decrease in peak heights and areas of asymmetric, symmetric C-H stretching, C=O stretching and amide bands. A split in amide II band was observed with iontophoresis. ATR-FTIR studies suggest conformational changes in the lipid-protein domains thereby increasing permeation. Histopathological studies on treated skin samples, gave an insight about the anatomical changes brought by the application of various enhancers. Binary mixture of menthol and ethanol in combination with square wave gave best results.

Acrylic Resins↗
PubMed2003

Quantitative analysis of protein adsorption on a planar surface by Fourier transform infrared spectroscopy: lysozyme adsorbed on hydrophobic silicon-containing polymer.

The adsorption of hen egg white lysozyme onto a solid polytris(trimethylsiloxy)silylstyrene (pTSS) surface from a D(2)O solution at pD 7 containing 100 mM NaCl and 10 mM sodium deuterated phosphate was monitored at 25 degrees C by Fourier transform infrared spectroscopy using the attenuated total reflection (ATR) method. The infrared spectrum attributed to only the adsorbed lysozyme was derived from the observed spectrum, and the amount of adsorbed lysozyme was determined as a function of time and lysozyme concentration. The kinetics of adsorption could be decomposed into two components, one of which was a process with a time constant of larger than 4 h(-1) and the other was a process with one of about 0.1 h(-1). These spectra showed that the lysozyme adsorbed in the faster process had a higher beta-structure content than the dissolved lysozyme. It was also found that the slower adsorption induced some conformational change in the lysozyme adsorbed in the faster process and/or that adsorbed in the slower process. After adsorption for 24 h, the pTSS surface was rinsed out with lysozyme-free solution. The resultant spectra of the surface indicated that the lysozyme adsorbed in the faster process was bound irreversibly on the surface and was changed to a conformer with a higher beta-structure content during the slower process. The experimental procedures and the theoretical applications for such a quantitative analysis in the ATR spectroscopic method are presented in detail.

Adsorption↗
PubMed2004

Effects of particle size on near-wall depletion in mono-dispersed colloidal suspensions.

In this work we investigate the change in particle concentration near a solid boundary for colloidal dispersions in pressure driven flow, commonly referred to as wall depletion. In particular we determine the effect of Peclet number on the strength and spatial extent of the depleted layer. The change in concentration near the solid boundary is measured with attenuated total reflection infrared (ATR-IR) spectroscopy described previously (P.J.A. Hartman Kok et al., J. Rheol. 46 (2002) 481). The method is capable of measuring the concentration of particles at distances ranging from 0.2 to 1.0 mum from the boundary. The suspensions investigated consisted of mono-dispersed polystyrene particles in water. Particles of four different sizes were used, with radius, a, of 30, 54, 105, and 197 nm. (The ratio H/a was in the range 2500-17,000 with H being the height of the flow cell.) This enabled us to measure the wall depletion effect over a wide range of Peclet numbers, ranging from 0.01 to 45. We found that wall depletion was not significant for Peclet numbers smaller than unity. Estimates of the wall slip layer thickness obtained from rheological experiments were consistent with the results obtained by ATR-IR spectroscopy.

Journal Article↗
PubMed2006

Combining kinetic investigation with surface spectroscopic examination to study the role of aromatic carboxyl groups in NOM adsorption by aluminum hydroxide.

The adsorption of a series of aromatic carboxylic acids, with different numbers and positions of carboxyl groups in the phenyl ring, on aluminum hydroxide was investigated with ATR-FTIR and kinetic analyses to verify the role of aromatic carboxyl groups in the surface complexation of NOM with aluminum hydroxide. It was revealed that the formation of outer-sphere complexes dominated the adsorption of most of the aromatic carboxylates over the pH range examined in this study. Inner-sphere complexes were only detected at some pH levels for some aromatic carboxylates adsorption. The aromatic carboxylates were most likely to be adsorbed onto the first surface layer of hydroxyl groups and water molecules without forming coordinative bonds with the aluminum hydroxide surfaces, but strong hydrogen bonds were formed in this process. The adsorption data fitted the pseudo-second-order kinetic model very well. The activation energies of adsorption calculated from the rate constants of pseudo-second-order kinetics agreed with the ATR-FTIR analysis that the aromatic carboxylates, except pyromellitate, were adsorbed predominantly as outer-sphere complexes on aluminum hydroxide at pH 7. This study revealed that phenolic groups may be more significant than carboxylic groups for the chemical adsorption of NOM onto minerals. The presence of additional carboxylic groups enhanced the adsorption considerably, while the enhancement was limited when there were three or four carboxylic groups on the phenyl ring. The adsorption of aromatic carboxylates was affected by the positions and pK(a) values of the donor groups and the solution pH.

Adsorption↗
PubMed2004

Mechanism of the synergic effects of calcium chloride and electroporation on the in vitro enhanced skin permeation of drugs.

We have already reported the substantial synergic effects of CaCl(2) and electroporation (EP) on in vitro skin permeation of calcein and FITC dextrans. In the present paper, we investigated the mechanisms for these effects by considering changes in lamellar structure and barrier recovery time of the biggest skin barrier, the stratum corneum, by this combined treatment. The change in skin lamellar structure was evaluated by lipid mobility in the stratum corneum using ATR-FTIR, calcein release from stratum corneum-lipid liposomes (SCLL), in vitro skin permeation of calcein and transepidermal water loss (TEWL). The ATR-FTIR measurement, in vitro skin permeation and changes in TEWL were also used for examining the barrier recovery time. The C-H stretching band of skin lipids produced with EP was blue-shifted when compared to that without EP. Asymmetric C-H stretching was highest with EP in CaCl(2) solution. Little release of calcein was observed from SCLL without EP, whereas higher releases were observed after EP with or without NaCl or CaCl(2). Particularly high calcein release (>20%) was observed over 60 min with EP in CaCl(2) solution. The in vitro permeation study of calcein was conducted through excised hairless rat skin that was pretreated with EP before skin excision. Permeation rate was highest in skin excised immediately after in vivo EP, and this rate decreased with time after EP treatment. TEWL recovered to control levels within 2 h after EP in distilled water or NaCl solution, whereas high TEWL was maintained after EP in CaCl(2) solution. These results suggest that at least lamellar destruction of stratum corneum must be related to the enhanced skin permeation of drugs by the combination of CaCl(2) and EPF. On the other hand, a prolonged enhancing effect on the skin permeation of calcein by this combination may be due to a high lamellar destruction and/or delayed barrier repair of stratum corneum.

Administration, Cutaneous↗
PubMed2005

Effect of L-menthol and 1,8-cineole on phase behavior and molecular organization of SC lipids and skin permeation of zidovudine.

The aim of this investigation was to study the effect of 1,8-cineole and L-menthol on phase behavior and molecular organization of Stratum corneum (SC) lipids and permeation of zidovudine (AZT) across human cadaver skin (HCS). Permeation studies were conducted across HCS using Franz diffusion cells at 37 degrees C. Differential scanning calorimetry (DSC) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were employed to understand the effect of terpenes on phase behavior and molecular organization of a model SC lipid system consisting of an equimolar mixture of ceramide, palmitic acid and cholesterol. Both 1,8-cineole and L-menthol applied at 5% w/v in 66.6% ethanol as a vehicle significantly enhanced the pseudosteady state flux of AZT across HCS. The vehicle reduced the number of endothermic transitions observed in the DSC thermogram of a hydrated model SC lipid system from three to two with a lowered midtransition temperature (Tm), while the inclusion of terpenes resulted in a single but very broad endothermic transition for the model SC lipid system. Correspondingly, ATR-FTIR studies revealed that both 1,8-cineole and L-menthol increased CH2 stretching frequencies on either side of lipid transition in addition to lowering the Tm of model SC lipid system by approximately 2-8 degrees C. The alterations observed in the amide-I frequencies of model SC lipid system after the inclusion of terpenes suggest that they disrupt the interlamellar hydrogen-bonding network at the polar head group region. Further, terpenes also increased the hydration levels of the lipid system probably by forming new aqueous channels. These results indicate that terpenes enhance transdermal permeation of AZT and other drugs by transforming SC lipids from a highly ordered orthorhombic perpendicular subcellular packing to a less ordered hexagonal subcell packing.

Animals↗
PubMed2005

The effect of different media on the survival and induction of stress responses by Campylobacter jejuni.

The survival kinetics of Campylobacter jejuni strain CI 120 to a challenge of pH 4.5 was studied in seven different media. A medium effect was observed, showing up to a 5-log difference in stress resistance of cells. Strain variation in survival of C. jejuni was observed in Brucella broth (BBL). The ability of C. jejuni CI 120 to respond to a stress after growth in seven different media was also examined. An Adaptive Tolerance Response (ATR) was induced in only three of the seven media tested. The degree of resistance induced by the ATR varied between the different media. The production, during growth, of an extracellular component that confers stress resistance against subsequent acid challenge was observed in only four of seven media tested. Due to the direct effect of medium on stress/survival of C. jejuni, the results suggest that studies using different media may not be comparable.

Campylobacter jejuni↗
PubMed2005

Genotoxic stress targets human Chk1 for degradation by the ubiquitin-proteasome pathway.

The Chk1 kinase is a major effector of S phase checkpoint signaling during the cellular response to genotoxic stress. Here, we report that replicative stress induces the polyubiquitination and degradation of Chk1 in human cells. This response is triggered by phosphorylation of Chk1 at Ser-345, a known target site for the upstream activating kinase ATR. The ubiquitination of Chk1 is mediated by E3 ligase complexes containing Cul1 or Cul4A. Treatment of cells with the anticancer agent camptothecin (CPT) triggers Chk1 destruction, which blocks recovery from drug-induced S phase arrest and leads to cell death. These findings indicate that ATR-dependent phosphorylation of Chk1 delivers a signal that both activates Chk1 and marks this protein for proteolytic degradation. Proteolysis of activated Chk1 may promote checkpoint termination under normal conditions, and may play an important role in the cytotoxic effects of CPT and related anticancer drugs.

Bromodeoxyuridine↗
PubMed2004

Infrared spectra of H(2)16O, H(2)18O and D(2)O in the liquid phase by single-pass attenuated total internal reflection spectroscopy.

Mid-infrared attenuated total internal reflection (ATR) spectra of H(2)16O, H(2)18O and D(2)16O in the liquid state were obtained and normal coordinate analysis was performed based on the potential energy surface obtained from density functional theory (DFT) calculations. Fits of the spectra to multiple Gaussians showed a consistent fit of three bands for the bending region and five bands for the stretching region for three isotopomers, H(2)16O, H(2)18O and D(2)16O. The results are consistent with previous work and build on earlier studies by the inclusion of three isotopomers and mixtures using the advantage of single-pass ATR to obtain high quality spectra of the water stretching bands. DFT calculation of the vibrational spectrum of liquid water was conducted on seven model systems, two systems with periodic boundary conditions (PBC) consisting of four and nine H(2)16O molecules, and five water clusters consisting of 4, 9, 19, 27 and 32 H(2)16O molecules. The PBC and cluster models were used to obtain a representation of bulk water for comparison with experiment. The nine-water PBC model was found to give a good fit to the experimental line shapes. A difference is observed in the broadening of the water bending and stretching vibrations indicative of a difference in the rate of pure dephasing. The nine-water PBC calculation was also used to calculate the wavenumber shifts observed in the water isotopomers.

Deuterium Oxide↗
PubMed2004

A comparison of human H295R and rat R2C cell lines as in vitro screening tools for effects on aromatase.

In this study we evaluated the rat Leydig cell carcinoma cell line R2C and the human adrenocorticocarcinoma cell line H295R for their suitability as in vitro screening tools for potential interference of xenobiotics with aromatase activity. A 24h exposure to prochloraz (PRO), fadrozole (FAD) and epoxyconazole (EPO) resulted in complete catalytic inhibition in H295R and R2C cells. In H295R cells, PRO and FAD were mixed-type inhibitors with apparent K(i) values of 0.04 and 0.03 microM, and apparent K(i)' values of 0.33 and 0.06 microM, respectively. EPO was a competitive inhibitor with an apparent K(i) value of 0.51microM. In R2C, all three compounds showed mixed type inhibition kinetics, with apparent K(i) values (microM) of 0.004, 0.003 and 0.07, and apparent K(i)' values (microM) of 0.41, 0.01 and 2.42, respectively. Exposure for 24h of H295R cells to 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP), prostaglandin E2 (PGE2), phorbol 12-myristate 13-acetate (PMA), or dexamethasone (DEX) resulted in 4.0, 2.8, 3.6 or 3.6-fold induction of aromatase activity, respectively, as well as in an increase of several human aromatase transcripts with promoter-specific 5'-ends (pII and I.3). In R2C cells, only PMA slightly induced aromatase activity. A 24h exposure of H295R cells to atrazine (ATR), resulted in a three-fold induction of aromatase activity and a slight increase in pII and I.3 aromatase transcripts. However, ATR did not induce aromatase activity in R2C cells. We conclude that the H295R cell line contains aromatase promoter regions, which are responsive to the respective stimulants. They play a role in aromatase regulation in various tissues such as brain, placenta, healthy and diseased gonadal and breast tissue and therefore, they may play an important role in tumor genesis, development, behavior and reproduction. The H295R cell line may therefore be a relevant and useful tool in risk assessment of xenobiotics. The R2C cell line, although not suitable for studying induction, appears to be a more sensitive cell line for studying inhibitory effects of xenobiotics on aromatase activity.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Autonomic dysfunction of rat jejunum submitted to cold ischemic preservation is prevented by heparin.

Previous studies suggest that cold ischemic preservation (CIP) employed in small bowel transplantation promotes loss of intestinal motility due to severe lesions in autonomic enteric nerves. This autonomic dysfunction may be prevented by antioxidant agents. In this work, we investigated whether preservation with heparin prevented autonomic dysfunction of rat jejunum submitted to CIP for a long time. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were preserved at 4 degrees C in Ringer's lactate solution without (-) or with (+) 100 UI/mL heparin (H). After preservation for 12 hours, H+ and H- preparations were mounted in parallel in isolated organ baths containing 10 mL Tyrode's solution at 37 degrees C for the study of neurogenic contractions evoked by electrical field stimulation (EFS; 10-30 Hz, 1-ms duration, 60 V) or by stimulation of nicotinic (NIC) or muscarinic (carbachol, CCh) cholinoceptors. The effects of NIC (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists were studied on these contractions. Contractions induced by EFS (30 Hz) were four times greater in H+ (1.02 +/- 0.12 g) versus H- (0.26 +/- 0.07 g), while contractions induced by NIC (1 mmol/L) were also four times higher in H+ (1.07 +/- 0.10 g) than H- (0.25 +/- 0.09 g) preparations. In addition, contractions induced by CCh (1 mmol/L) were two times higher in H+ (1.21 +/- 0.13 g) than in H- (0.65 +/- 0.10 g). EFS, NIC, and CCh contractions were inhibited by pretreatment of jejunum with HEX or ATR (1 mumol/L/30 min), in H+ and H-. These results indicated that addition of heparin to a preservation solution attenuated the autonomic dysfunction of rat jejunum submitted to CIP for a long time.

Animals↗
PubMedDate not supplied

Atenolol attenuates autonomic dysfunction of rat jejunum submitted to cold ischemic preservation.

In vitro studies have demonstrated that cold ischemic preservation (CIP) employed in small bowel transplantation produces loss of intestinal motility due to severe lesions of autonomic enteric nerves and that this autonomic dysfunction is attenuated by antioxidant agents. In this work, we investigated whether preservation with atenolol attenuated autonomic dysfunction of rat jejunum submitted to long-term CIP. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were surgically isolated and preserved at 4 degrees C in Ringer's lactate solution without (-) or with (+) 1 mumol/L atenolol (AT). After preservation for 12 hours, AT+ and AT- preparations were mounted in parallel in isolated organ baths containing 10 mL Tyrode's solution at 37 degrees C for the study of neurogenic contractions evoked by electrical field stimulation (EFS; 10 to 30 Hz, 1-ms duration, 60 V) or by stimulation with nicotinic (nicotine, NIC) or muscarinic (carbachol, CCh) cholinoceptor agents as well as nicotine (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists. Contractions induced by EFS (30 Hz) were 46% higher in AT+ (0.38 +/- 0.02 g) than AT- (0.26 +/- 0.01 g), while contractions induced by NIC (1 mmol/L) were 84% higher in AT+ (0.46 +/- 0.03 g) than in AT- (0.25 +/- 0.02 g). In addition, contractions induced by CCh (1 mmol/L) were 34% higher in AT+ (0.87 +/- 0.06 g) than in AT- (0.65 +/- 0.08 g). EFS-, NIC-, and CCh-induced contractions were inhibited by pretreatment of jejunum with HEX or ATR (1 mumol/30 min), in AT+ and AT-. These results suggest that addition of atenolol in the preservation solution attenuated autonomic dysfunction of rat jejunum submitted to long-term CIP.

Adrenergic beta-Antagonists↗
PubMed2003

P21 response to DNA damage induced by genistein and etoposide in human lung cancer cells.

The p21(WAF1/Cip1) gene plays a central role in cell cycle regulation. Here we show that topoisomerase II inhibitors, genistein and etoposide, induce p21(WAF1/Cip1) expression mainly in a p53-dependent manner in human lung cancer cell line A549. However, although p53 accumulated, p21(WAF1/Cip1) expression did not depend on the level of Ser15 phosphorylation of p53. Caffeine, an ataxia telangiectasia-mutated (ATM), and ATM- and Rad3-related kinase (ATR) inhibitor, abrogated genistein-induced p21(WAF1/Cip1) and largely blocked etoposide-induced p21(WAF1/Cip1) expression. Wortmannin, an ATM- and DNA-dependent protein kinase inhibitor, partially inhibited p21(WAF1/Cip1) expression induced by genistein and etoposide, whereas UCN-01, a Chk1 inhibitor, partially blocked etoposide, but not genistein-induced p21(WAF1/Cip1) expression. These data suggest that both genistein and etoposide induce p21(WAF1/Cip1) expression in a p53-dependent manner. Genistein appears to stimulate p21(WAF1/Cip1) expression through p53 via ATM, whereas etoposide may activate both ATM and ATR pathways. Our results suggest different mechanisms participate in genistein and etoposide induced p21(WAF1/Cip1) expression.

Antineoplastic Agents↗
PubMed2001

Membrane molecule reorientation in an electric field recorded by attenuated total reflection Fourier-transform infrared spectroscopy.

Electric fields play an important role in the physiological function of macromolecules. Much is known about the role that electric fields play in biological systems, but membrane molecule structure and orientation induced by electric fields remain essentially unknown. In this paper, we present a polarized attenuated total reflection (ATR) experiment we designed to study the effect of electric fields on membrane molecule structure and orientation by Fourier-transform infrared (FTIR) spectroscopy. Two germanium crystals used as the internal reflection element for ATR-FTIR experiments were coated with a thin layer of polystyrene as insulator and used as electrodes to apply an electric field on an oriented stack of membranes made of dioleylphosphatidylcholine (DOPC) and melittin. This experimental set up allowed us for the first time to show fully reversible orientational changes in the lipid headgroups specifically induced by the electric potential difference.

Biophysical Phenomena↗
PubMed1991

Orientation of melittin in phospholipid bilayers. A polarized attenuated total reflection infrared study.

The helical order parameter of the 26-residue amphiphilic bee venom peptide melittin was measured by polarized attenuated total reflection infrared spectroscopy (ATR-IR) in dry phospholipid multibilayers (MBLs) and when bound to single supported planar bilayers (SPBs) under D2O. Melittin adopted an alpha-helical conformation in MBLs of dipalmitoyl-phosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), a 4:1 mixture of POPC and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), and when bound to SPBs of POPC:POPG (4:1). The order parameter of the alpha-helix in the bilayers depended mainly on the type of membrane preparation, and only little on the phospholipid composition of the bilayers. On hydrated SPBs, the helical order parameter was negative, indicating that the alpha-helix long axis of melittin was preferentially oriented parallel to the plane of the supported membrane. However, in dry MBLs, the helical order parameter was positive, indicating that the alpha-helix of melittin was preferentially oriented parallel to the phospholipid fatty acyl chains. It is concluded that the orientation of melittin in membranes depends on the degree of hydration of the model membranes rather than on the technique which is used for its determination. ATR-IR spectroscopy of polypeptides in or associated with supported planar membranes in D2O may become a useful tool for the determination of their orientation in and on membranes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Oriented 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine/ganglioside membranes: a Fourier transform infrared attenuated total reflection spectroscopic study. Band assignments; orientational, hydrational, and phase behavior; and effects of Ca2+ binding.

Fourier transform infrared (FTIR) attenuated total reflection (ATR) spectroscopy was used to elucidate the hydration behavior and molecular order of phospholipid/ganglioside bilayers. We examined dry and hydrated films of the gangliosides GM1, deacetyl-GM1, lyso-GM1, deacetyllyso-GM1, and GM3 and oriented mixed films of these gangliosides with 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) using polarized light. Analysis of the amide I frequencies reveals that the amide groups are involved in intermolecular interactions via hydrogen bonds of varying strengths. The tilt angle of the acyl chains of the lipids in mixed films was determined as a function of ganglioside structure. Deacetylation of the sialic acid in the headgroup has a stronger influence on the tilt angle than the removal of the ganglioside fatty acid. The phase behavior was examined by FTIR ATR spectroscopy and by differential scanning calorimetry (DSC) measurements on lipid suspensions. At the same molar concentration, lyso-gangliosides have less effect on changes of transition temperature compared to the double-chain analogs. Distinct differences in the amide band shapes were observed between mixtures with lyso-gangliosides and normal double-chain gangliosides. Determined from the dicroic ratio RATR, the orientation of the COO- group in all DMPC/ganglioside mixtures was found to be relatively fixed with respect to the membrane normal. In 4:1 mixtures of DMPC with GM1 and deacetyl-GM1, the binding of Ca2+ leads to a slight decrease in chain tilt in the gel phase, probably caused by a dehydration of the membrane-water interface. In mixtures of DMPC with GM3 and deacetyl-lyso-GM1, a slight increase in chain tilt is observed. The chain tilt in DMPC/lyso-GM1 mixtures is unchanged. Analysis of the COO- band reveals that Ca2+ does not bind to the carboxylate group of the sialic acid of GM1 and deacetyl-GM1, the mixtures in which a decrease in chain tilt was observed. Binding to the sialic acid was only observed for mixtures of DMPC with GM3, lyso-GM1, and deacetyl-lyso-GM1. Ca2+ obviously accumulates at the bilayer-water interface and leads to partial dehydration of the headgroup region in the gel as well as in the liquid-crystalline phase. This can be concluded from the changes in the amide I band shapes. With the exception of DMPC/deacetyl-GM1, the effects on the ester C==O bands are small. The addition of Ca2+ has minor effects on the phase behavior, with the exception of the DMPC/GM1 mixture.

Animals↗