排序方式: 共有19条查询结果,搜索用时 31 毫秒
1.
Summary Physical parameters of membrane bilayers were studied for their effect on the binding of hematoporphyrin derivative (Hpd), which is used as a sensitizer in photodynamic therapy of cancerous tissues. The purpose of this study was to clarify which parameters were relevant, under physiological conditions, to the selectivity of Hpd binding to cancer cells. Fluorescence spectroscopy was used to measure the relative partitioning of the dye between the lipid and aqueous media. Increasing the microviscosity of the liposomes' membranes by various bilayer additives results in a strong reduction of Hpd binding, to an extent independent of the specific additive. The effect of temperature near the physiological value as well as the effect of cross membrane potential are small. Surface potential does not affect the binding constant, indicating that the binding species does not carry a net electric charge. 相似文献
2.
3.
光敏反应对过氧化氢酶的影响 总被引:1,自引:0,他引:1
林植芳 《生物化学与生物物理进展》1991,18(6):435-438
光氧化反应中,纯过氧化氢酶活性受光敏化剂血卟啉Ⅳ和核黄素的抑制。随光敏化剂浓度增高及照光时间延长,抑制程度加大。酶与光敏化剂反应后吸收光谱位移,峰形改变。紫外差示吸收光谱出现229nm负峰(血卟啉)和236—240nm峰(核黄素)。结果表明酶活的抑制与其蛋白构象的变化相关。 相似文献
4.
Dalal A. Al-Mutairi James D. Craik Ines Batinic-Haberle Ludmil T. Benov 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
Cell proliferation is notably dependent on energy supply and generation of reducing equivalents in the form of NADPH for reductive biosynthesis. Blockage of pathways generating energy and reducing equivalents has proved successful for cancer treatment. We have previously reported that isomeric Zn(II) N-methylpyridylporphyrins (ZnTM-2(3,4)-PyP4+) can act as photosensitizers, preventing cell proliferation and causing cell death in vitro. The present study demonstrates that upon illumination, ZnTM-3-PyP inactivates glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, NADP+ -linked isocitrate dehydrogenase, aconitase, and fumarase in adenocarcinoma LS174T cells. ZnTM-3-PyP4+ was significantly more effective than hematoporphyrin derivative (HpD) for inactivation of all enzymes, except aconitase and isocitrate dehydrogenase. Enzyme inactivation was accompanied by aggregation, presumably due to protein cross-linking of some of the enzymes tested. Inactivation of metabolic enzymes caused disruption of cancer cells' metabolism and is likely to be one of the major reasons for antiproliferative activity of ZnTM-3-PyP. 相似文献
5.
Porphyrin depth in lipid bilayers as determined by iodide and parallax fluorescence quenching methods and its effect on photosensitizing efficiency 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Bronshtein I Afri M Weitman H Frimer AA Smith KM Ehrenberg B 《Biophysical journal》2004,87(2):1155-1164
Photosensitization by porphyrins and other tetrapyrrole chromophores is used in biology and medicine to kill cells. This light-triggered generation of singlet oxygen is used to eradicate cancer cells in a process dubbed "photodynamic therapy," or PDT. Most photosensitizers are of amphiphilic character and they partition into cellular lipid membranes. The photodamage that they inflict to the host cell is mainly localized in membrane proteins. This photosensitized damage must occur in competition with the rapid diffusion of singlet oxygen through the lipid phase and its escape into the aqueous phase. In this article we show that the extent of damage can be modulated by employing modified hemato- and protoporphyrins, which have alkyl spacers of varying lengths between the tetrapyrrole ring and the carboxylate groups that are anchored at the lipid/water interface. The chromophore part of the molecule, and the point of generation of singlet oxygen, is thus located at a deeper position in the bilayer. The photosensitization efficiency was measured with 9,10-dimethylanthracene, a fluorescent chemical target for singlet oxygen. The vertical insertion of the sensitizers was assessed by two fluorescence-quenching techniques: by iodide ions that come from the aqueous phase; and by spin-probe-labeled phospholipids, that are incorporated into the bilayer, using the parallax method. These methods also show that temperature has a small effect on the depth when the membrane is in the liquid phase. However, when the bilayer undergoes a phase transition to the solid gel phase, the porphyrins are extruded toward the water interface as the temperature is lowered. These results, together with a previous publication in this journal, represent a unique and precedental case where the vertical location of a small molecule in a membrane has an effect on its membranal activity. 相似文献
6.
Valeria Petronilli Alessandra Zulian Giulio Jori Giuseppe Tognon Paolo Bernardi 《BBA》2009,1787(7):897-172
We have studied the mitochondrial permeability transition pore (PTP) under oxidizing conditions with mitochondria-bound hematoporphyrin, which generates reactive oxygen species (mainly singlet oxygen, 1O2) upon UV/visible light-irradiation and promotes the photooxidative modification of vicinal targets. We have characterized the PTP-modulating properties of two major critical sites endowed with different degrees of photosensitivity: (i) the most photovulnerable site comprises critical histidines, whose photomodification by vicinal hematoporphyrin causes a drop in reactivity of matrix-exposed (internal), PTP-regulating cysteines thus stabilizing the pore in a closed conformation; (ii) the most photoresistant site coincides with the binding domains of (external) cysteines sensitive to membrane-impermeant reagents, which are easily unmasked when oxidation of internal cysteines is prevented. Photooxidation of external cysteines promoted by vicinal hematoporphyrin reactivates the PTP after the block caused by histidine photodegradation. Thus, hematoporphyrin-mediated photooxidative stress can either inhibit or activate the mitochondrial permeability transition depending on the site of hematoporphyrin localization and on the nature of the substrate; and selective photomodification of different hematoporphyrin-containing pore domains can be achieved by fine regulation of the sensitizer/light doses. These findings shed new light on PTP modulation by oxidative stress. 相似文献
7.
A G Sedee G M Beijersbergen van Henegouwen N J De Mol G Lodder 《Chemico-biological interactions》1984,51(3):357-363
The interaction with DNA of [4-14C]oestrone upon photosensitization with hematoporphyrin (HP) as a photosensitizer has been investigated. By means of Sephadex LH-20 gel filtration and extraction with dichloromethane it was found that, after irradiation (lambda greater than 425 nm) of a solution of HP, DNA and [4-14C]oestrone 21% of the radiolabel was associated with DNA. If DNA was added after irradiation 23% was bound to DNA, whereas 25% of the oestrone remained after photoreaction under the conditions applied. The binding occurs via the reactive 10 beta-hydroperoxy-1,4-estradien-3,17-dione, which is the only product after photosensitization of oestrone. The hydroperoxide has a strong interaction with DNA compared with that of other steroids. By repeated precipitation with 5 M NaCl and ethanol the association can be broken. It is reported, that binding of oestrone to protein induced by both photosensitization and horseradish peroxidase (HRPO)/H2O2 is irreversible, but that the amount of binding to DNA is dependent on the method of determination. However, neither the hydroperoxide nor its reduced product, a p-quinol, is intermediate or product in the HRPO catalyzed reaction of oestrogens. The tight association of the hydroperoxide product of oestrone with DNA, which may proceed via hydrogen bonding between the -OOH group and oxygen atoms of the backbone phosphate groups or of the furanose ring, might be a cause of chemical modification of DNA and of mutagenic effects. 相似文献
8.
光敏剂HpD和单态氧探针FCLA的跨膜效率及其亚细胞定位研究 总被引:1,自引:0,他引:1
化学发光探针分子FCLA是一种海萤荧光素类似物分子,它可以选择性地与1O2及O2.反应产生化学发光,近年来已被成功用于在组织水平上进行光动力学和声动力学的肿瘤诊断中。但是FCLA在生物样品中能否进入细胞以及在细胞内的定位等问题目前尚不清楚。本文中报道利用激光共焦扫描显微镜进行FCLA和HpD的跨膜效率以及细胞内定位的形态学研究初步结果。结果表明,在37℃培养箱中用完全培养液进行培养时发现,HpD和FCLA都可以有效地跨膜,并定位在细胞质中。虽然FCLA与HpD的分子量大小相近,但是其进入肿瘤细胞的效率却并不相同。与HpD相比FCLA更容易进入细胞,对细胞没有明显的毒性。实验中未观测到FCLA和HpD进入细胞核的证据。本研究为利用1O2和O2.探针FCLA动态观测细胞内1O2或O2.的产生和定位建立了实验基础,并将推动在细胞或亚细胞水平上进行光动力学机制以及光敏过程引起细胞凋亡机制的研究。 相似文献
9.
A G Sedee G M Beijersbergen van Henegouwen K J Lusthof G Lodder 《Biochemical and biophysical research communications》1984,125(2):675-681
Recent studies have established that polypeptide growth factors cause an elevation of the cytoplasmic pH (pHi) in cultured mammalian cells by stimulating Na+/H+ exchange. We show that vanadate, previously found to act as a mitogen for a number of cells, reversibly activates Na+/H+ exchange at micromolar concentrations in A431 cells, leading to a large increase of pHi. The stimulation of Na+/H+ exchange by vanadate is not due to inhibition of the Na+/K+ ATPase and is unrelated to possible effects of vanadate on cAMP levels. Elevation of pHi by vanadate and by epidermal growth factor (EGF) both display similar kinetics, and both EGF and vanadate stimulate the rate of pHi recovery following an acute acid load, suggesting that vanadate stimulates Na+/H+ exchange by a mechanism similar to that of polypeptide growth factor stimulation. Thus, stimulation of Na+/H+ exchange may be a common property not only of polypeptide growth factors but also of other, chemically unrelated mitogens. 相似文献
10.
The influence of protoporphyrin IX derivatives—2,4-di(1-methoxyethyl)-deuteroporphyrin IX disodium salt (dimegin) and hematoporphyrin
IX (HP)—on the activation of human platelet soluble guanylate cyclase by sodium nitroprusside was investigated. Dimegin and
HP, like 1-benzyl-3-(hydroxymethyl-2-furyl)indazole (YC-1), produce synergistic effects on the activation of soluble guanylate
cyclase by sodium nitroprusside. The synergistic activation of the enzyme by the combination of 10 μM sodium nitroprusside
and 5 μM dimegin (or 5 μM HP) was 190 ± 19 and 134 ± 10%, respectively. The synergistic activation of guanylate cyclase by
3 μM YC-1 and 10 μM sodium nitroprusside was 255 ± 19%. Dimegin and HP had no effect on the activation of guanylate cyclase
by YC-1; they did not change the synergistic effect of YC-1 (3 μM) and sodium nitroprusside (10 μM) on guanylate cyclase activity.
The synergistic activation of NO-stimulated guanylate cyclase activity by dimegin and HP represents a new biochemical effect
of these compounds that may have important pharmacotherapeutic and physiological significance.
Published in Russian in Biokhimiya, 2006, Vol. 71, No. 3, pp. 426–431. 相似文献