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S B Hwang

Publications and source records attributed to S B Hwang.

62 records · Page 4Linked to original sources
PubMed1981

Membrane effects of antiinflammatory agents. 2. Interaction of nonsteroidal antiinflammatory drugs with liposome and purple membranes.

The interaction of the nonsteroidal antiinflammatory drugs (NSAIDS) indomethacin, diflunisal, and flurbiprofen and the active sulfide metabolite of sulindac with phosphatidylcholine (PC) liposomes was investigated using differential scanning calorimetry (DSC). These biologically active structures decrease the phase transition temperature and broaden the transition peak with increasing concentration, but without affecting the enthalpy change for the transition on the thermal scan. A comparison with the effects of the prodrug sulindac and its inactive sulfone metabolite suggests that the main action of NSAIDS on membranes is a reduction of the cooperative interaction between phospholipid molecules. The probable positions of these compounds in the bilayer are inferred from similar DSC effects of several reference compounds whose mode of binding to the PC bilayer have previously been described. The active antiinflammatory structures appear to insert deeply into the hydrocarbon region of the bilayer, whereas the inactive compounds probably bind mainly to the carbonyl region near the surface. Using purple membrane as a model to study the drug effect on protein--protein interaction in this membrane system, low concentrations of active NSAIDS effectively dissociate the bacteriorhodopsin lattice. These results suggest that the active NSAIDS studied here are able to partition deeply into the hydrocarbon region of the bilayer and interact with a membrane protein imbedded inside the bilayer. The prodrug sulindac per se is devoid of any significant membrane effects.

Anti-Inflammatory Agents↗
PubMed1980

Proton transport by bacteriorhodopsin in planar membranes assembled from air-water interface films.

Bacteriorhodopsin, in known amounts and controlled orientation, is incorporated into planar membrane films. These films are formed by the sequential transfer of two air-water interface films onto a thin, hydrophilic, electrically conductive support cast from nitrocellulose. The films are easily accessible to electrical measurements and to control of the ionic milieu on either side of the membrane. The area of the assembled membrane films can be varied between 2.3 x 10(-2) cm2 and 0.7 cm2. Illumination of these films produces photocurrents, photovoltages, and changes in the pH of the surrounding medium. The peak amplitude of the photocurrent increases linearly with light intensity for dim lights, and it approaches a saturating value for brighter lights. In the linear range, the stoichiometry of transport is 0.65 +/- 0.06 protons/absorbed photon. The rate of transport is linearly proportional to light at all intensities tested. The amplitude and kinetics of the photovoltage measured are accurately predicted by the photocurrent generated and the passive electrical features of the film. Parallel measurements of pH and photocurrent reveal that the light-induced changes in pH are fully accounted for by the rate and amount of charge transport across the membrane. Preceding the transport of protons, a transient photovoltage is detected that exhibits no detectable latency, reaches peak in about 80 microseconds, and probably arises from light-induced intramolecular charge displacements.

Air↗
PubMed1978

Transient photovoltages in purple membrane multilayers. Charge displacement in bacteriorhodopsin and its photointermediates.

The photovoltaic properties of bacteriorhodopsin molecules and their photochemical intermediates have been investigated in an experimental cell consisting of multilayered films of highly oriented, dry fragments of purple membrane and lipid sandwiched between two metal (Pd) electrodes. The electrical time constant of these sandwich cells containing between 5 and 30 layers is less than 10(-5) S. Bright illumination of these cells with actinic flashes of approximately 1 ms duration generates transient photovoltages. These photovoltages, which make the extracellular surface of purple membrane positive with respect to the intracellular surface, follow the time course of the flash with no detectable latency. The amplitude of the photovoltages increases linearly with light intensity and their action spectrum matches the absorption spectrum of the light-adapted state of bacteriorhodopsin, BR570. In these dry multilayer cells, the slow photointermediates of bacteriorhodopsin, M412, N520 and O640 are long lived. Illumination of the sandwich cells with long duration (200 ms) pulses of light results, therefore, in the formation of photomixtures containing all these slow photointermediates. Flash illumination of the sandwich cells immediately following the conditioning pulse produces photovoltages whose action spectra match the absorption spectra of the M412 and N520 photointermediates. The M412 photovoltages, like the BR570 photovoltages, follow the time course of the actinic flash with no detectable latency and increase in amplitude linearly with light intensity. But, unlike the BR570 photovoltage, the M412, N520 and O640 photovoltages make the extracellular surface of purple membrane negative with respect to the intracellular surface. Through the of their specific photovoltaic signals, M412 and N520 are shown to be kinetically distinct photointermediates of bacteriorhodopsin. Detection of fast photovoltages with these characteristics in the absence of any ionic solution, and in parallel with spectrophotometric changes, suggest that they arise from charge displacements in the bacteriorhodopsin molecules and their photointermediates as they undergo photochemical conversion in response to the absorption of photons.

Bacteriorhodopsins↗
PubMed1977

Structural and spectroscopic characteristics of bacteriorhodopsin in air-water interface films.

A suspension of purple membrane fragments in a solution of soya phosphatidyl-choline in hexane is spread at an air-water interface. Surface pressure and surface potential measurements indicate that the membrane fragments and lipids organize at the interface as an insoluble film. Electron microscopy of shadow-cast replicas of the film reveal that in the bacteriorhodopsin to soya PC weight ratio range of 2:1 to 10:1, these films consist of nonoverlapping membrane fragments which occupy approximately 35% of the surface area and are separated by a lipid monolayer. Furthermore, the membrane fragments are oriented with their intracellular surface towards the aqueous subphase. Nearly all the bacteriorhodopsin molecules at the interface are spectroscopically intact and exhibit visible spectral characteristics identical to those in aqueous suspensions of purple membrane and in intact bacteria. In addition, bacteriorhodopsin in air-dried interface films show spectral changes upon dark-adaptation and upon flash illumination similar to those observed in aqueous suspensions of purple membrane, but with slower kinetics. The kinetics of the spectral changes in interface films can be made nearly the same as in aqueous suspension by immersing the films in water.

Air↗
PubMed1977

Proton transport by bacteriorhodopsin through an interface film.

Interface films of purple membrane and lipid containing spectroscopically intact and oriented bacteriorhodopsin have been used as a model system to study the function of this protein. Small positive charges in surface potential (less than 1 mV) are detected upon illumination of these films at the air-water interface. These photopotentials are not affected by overlaying the interface film with a thin layer (0.3 mm) of decane. However, they are dramatically increased when lipid soluble proton carriers FCCP or DNP are added to the decane. The polarity of the photopotential indicates that, in the light, positive charges are transported through the interface from the aqueous to the organic phase. The action spectrum of the photopotential is identical to the absorption spectrum of bacteriorhodopsin. Since bacteriorhodopsin molecules are oriented with their intracellular surface towards the aqueous subphase, the characteristics of the photopotential indicate that in the light bacteriorhodopsin translocates protons from its intracellular to its extracellular surface. The kinetics of the photopotential reveal that the rate and extent of proton transport are proportional both to the fraction of bacteriorhodopsin molecules excited and to the concentration of proton acceptor. The photopotentials result from changes in the ionic distribution across the decane-water interface and can be cancelled by lipid soluble anions.

Air↗
PubMed1977

Purple membrane vesicles: morphology and proton translocation.

Purple membrane vesicles prepared by different techniques differ widely in their morphology and ability to establish a proton gradient in the light. The procedures used to prepare active vesicles do not completely dissociate the purple membrane and thus preserve a preferential orientation of the protein, while most of the lipid is exchanged for added lipid. Responses to illumination are largely determined by the size of the vesicles and the degree to which bacteriorhodopsin is preferentially oriented. Any attempt to compare the interaction of different lipids with bacteriorhodopsin by measuring the pH response must take these factors into account. With an improved technique we have obtained vesicles of rather uniform size and bacteriorhodopsin orientation, which accumulate protons with an initial rate of 160 ng H+ sec-1 mg-1 protein at light intensities of 10(6) erg cm-2 sec-1. The kinetics of the process are complex and at present insufficiently understood.

Bacteriorhodopsins↗
PubMedDate not supplied

Specific receptors of platelet-activating factor, receptor heterogeneity, and signal transduction mechanisms.

Platelet-activating factor (PAF) exerts its actions through the activation of specific PAF receptors found in a variety of cells and tissues. The signal transduction process induced by PAF appears to be modulated by guanine nucleotide-regulatory proteins (G-proteins) in both rabbit and human platelets and also in human polymorphonuclear leukocytes (PMNs). The PAF receptor, the G-protein coupled to the receptor, and the signal transduction mechanisms in human platelets are different from those in human PMNs. The PAF receptor in human PMNs may also be different from that in human eosinophils. The existence of receptor heterogeneity in guinea pig eosinophils is also proposed. Thus PAF receptor subtypes do exist. Further investigations are required to understand the role of each individual PAF receptor subtype.

Animals↗