共查询到20条相似文献,搜索用时 46 毫秒
1.
B Isomaa 《Biochemical pharmacology》1979,28(7):975-980
The interactions of ahomologue series of surface-active alky Itrimethylammonium salts (C10-C20) with the rat erythrocyte membrane were studied. The surfactants were found to have a biphasic effect on the erythrocyte membrane. At low concentrations they protected or stabilized erythrocytes against hypotonic haemolysis, but at higher concentrations they caused rapid haemolysis. The stabilizing and lytic effect increased with an increase in length of the alkyl chain to maximum activity at about C16. It is suggested that laminar-micellar transitions in the lipid bilayer of the membrane are responsible for the lytic activity of the surfactants. Micellar regions in the lipid bilayer abolish the ability of the membrane to prevent the free exchange of ions, and haemolysis of the cell results from a secondary osmotic effect. The stabilizing effect, on the other hand, is proposed to stem from an expansion of the membrane caused by a fluidizing effect of the surfactants on the lipid bilayer. Binding studies with the C16 homologue revealed that at a concentration causing 50 per cent haemolysis in an isotonic solution there are about 780,000 molecules bound per μm2 of the erythrocyte membrane. At a concentration giving 50 per cent protection against hypotonic haemolysis, the number of molecules bound per μm2 of the erythrocyte membrane was estimated to be 190,000. 相似文献
2.
Denis Daveloose Magali Sablayrolles Daniel Molle François Leterrier 《Biochemical pharmacology》1982,31(24):3949-3954
The membrane effects of ticlopidine on the erythrocyte membrane were explored by the spin label method at the proteic and phospholipidic levels. This spectroscopic study was completed by polyacrylamide gel electrophoresis of proteins, measurement of the protection against haemolysis and observation of the erythrocyte shape changes induced by the drug. Two types of effects have been observed. At concentrations higher than 5 × 10?4 M, ticlopidine is a weak denaturating agent of the membrane proteins. At concentrations of pharmacological interest, the main effect of the drug is a protection against hypotonic haemolysis, and an increase in the fluidity of the membrane phospholipidic core. This last result could explain in part the interesting pharmacological effect of ticlopidine on various circulatory troubles. 相似文献
3.
Quercetin is a naturally occurring flavonoid that exerts multiple pharmacological effects. In our previous study, we showed that quercetin greatly affects the lipid membrane. In this report, a study of quercetin on human erythrocyte membrane has been performed to determine the influence of this flavonoid on the fluidity and the conformational changes of membrane proteins. An additional aim of the study was to find how quercetin presence affects the resistance of membrane to haemolytic agents. The results showed that incorporation of quercetin into the erythrocyte membranes caused the changes of the partition coefficient of the Tempo spin label between the water and polar head group phases. In the studies, the W/S ratio has been used as a monitor of changes in protein conformation and in the environment within the membrane. It was observed that quercetin caused an increase in protein-protein interactions in human erythrocyte membranes. Haemolytic action of quercetin in the dark was also investigated. This compound showed protective effect against hypotonic haemolysis. However, in the heat-induced haemolysis quercetin caused acceleration of haemolysis. Dark reaction of erythrocyte with quercetin resulted in a shrinkage of the cells and alteration of their shapes. From the results we have concluded that modification of erythrocyte membrane by quercetin proceeds via reaction with membrane lipids and proteins. 相似文献
4.
Jrn Erik Jensen 《Basic & clinical pharmacology & toxicology》1976,38(5):465-473
Abstract The effect of chlorhexidine (Chx) and cetrimonium bromide (Ctab) on the haemolysis of erythrocytes has been studied. A concentration dependent release of haemoglobin was observed in isotonic media, with total haemolysis at 80 nmol Chx per 107 cells and 20 nmol Ctab per 107 cells. The rate of haemolysis induced by Chx shows a biphasic pattern in contrast to the uniphasic pattern of Ctab. In concentrations below 10 nmol per 107 cells, Chx produces more haemolysis than Ctab whereas the opposite effect is observed at higher concentrations. Chx and Ctab stabilize the erythrocyte membrane against hypotonic shock. The concentrations of Chx and Ctab giving maximal stabilization are 0.25 nmol per 107 cells and 2 nmol per 107 cells respectively. The normal biconcave disc form of the erythrocytes is converted to cup forms and in-vaginated spheres by Chx and Ctab. The binding of Chx to erythrocytes in isotonic media increases linearly with the total concentration up to about 25 nmol Chx per 107 cells where the curve has a point of inflection. With more than 25 nmol Chx per 107 cells the amount of Chx bound again increases linearly up to 120 nmol per 107 cells. The slope of the curve above the point of inflection is approximately 4 times that of the curve below this point. No level of saturation of the binding is observed at the concentrations of Chx used in this study. The mode of action of Chx on erythrocyte membranes is discussed in the light of the present results. 相似文献
5.
AKIYOSHI HARA NOBUMASA HAYASE HIROKO HASHIZUME YASUSHI ABIKO 《The Journal of pharmacy and pharmacology》1997,49(8):806-811
The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-l -carnitine (PAL-CAR) or palmitoyl 1-α-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 μm , respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 μm ) but not at the highest concentration used (1 mm ). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 μm to 1 mm . Similarly, dilazep (1 to 100 μm ) and K-7259 (1 μm to 1 mm ) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 μm , did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis). These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance. 相似文献
6.
The effects of promazine and thioridazine on hypotonic haemolysis of human erythrocytes are compared with their effect on Na+-K+-ATPase of washed human erythrocyte ghosts. Promazine (5 × 10-5 - 5 × 10-4 M) and thioridazine (10-5 - 10-4 M) stabilize erythrocytes against hypotonic haemolysis, but have lytic effects at higher concentrations. Both drugs inhibit Na+-K+-ATPase of erythrocyte membranes. This inhibition is slight at drug concentrations which have a membrane-stabilizing action, but is complete and irreversible at lytic concentrations of the drugs. Promazine and thioridazine also inhibit Na+-K+-ATPase in a membrane fraction prepared from rat hearts. The relative order of potency of the two drugs in this respect does not reflect their relative potency as general cardiac depressants. It is concluded that Na+-K+-ATPase is not a primary target for the action of promazine and thioridazine in the rat heart. It is suggested that inhibition of Na+-K+-ATPase by these agents is secondary to more general alterations of the physical properties of the cell membrane. 相似文献
7.
Eun Kyoung Choi Hae Dong Kim Eun Jung Park Seuk Young Song Tien Thuy Phan Miyoung Nam Minjung Kim Dong-Uk Kim Kwang-Lae Hoe 《Biomolecules & therapeutics.》2023,31(2):219
Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOP-induced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects. 相似文献
8.
Permeation Characteristics of 8-Methoxypsoralen Through Human Skin; Relevance to Clinical Treatment*
A. N. C. ANIGBOGU A. C. WILLIAMS B. W. BARRY 《The Journal of pharmacy and pharmacology》1996,48(4):357-366
The permeation characteristics through human skin of 8-methoxypsoralen (8-MOP) and its physical attributes were investigated. The log octanol/water partition coefficient and saturated aqueous solubility of 8-MOP at 32°C were 1.98 and 55.8 μg mL?1 respectively. 8-MOP showed Fickian diffusion, with its flux being linearly related to the concentration of drug in the donor solution. The permeability coefficient of 8-MOP through human skin from different concentrations of aqueous solutions and a 2.6 μg mL?1 bath lotion (as used in clinics) were statistically identical with mean values of 1.76 ± 0.12 × 10?2 and 1.70 ± 0.32 × 10?1 cm h?1 respectively (P ≥ 005). An ethanol/water (1:1 w/v) receptor solution did not improve the clearance of 8-MOP from the dermis when compared with an aqueous vehicle. Complete removal of the stratum corneum by tape stripping from full-thickness membranes produced a threefold increase in the flux of 8-MOP thus suggesting that the main barrier to 8-MOP permeation resides in the stratum corneum although the aqueous epidermal and dermal tissue provide a significant resistance to transdermal drug permeation. The equilibrium uptake of 8-MOP into psoriatic plaques and the 8-MOP aqueous/plaque partition coefficient were found to be more than twofold greater than for normal stratum corneum. The absorption of 8-MOP from the total applied topical dose (396 mg) was assessed as ~0.25% and only 2.5% of an oral dose, a significant reduction in the possible toxic hazard. The peak concentration of 8-MOP permeating through the skin was observed at about 35 min after limited exposure for 15 min. Our results suggest that following a 15 min bath in the drug solution, there may be a need for an interval of about 20 min before patients are irradiated to ensure the optimization of photosensitizer with UVA irradiation (PUVA) therapy. Alternatively, UV irradiation could be applied at a lower flux over a longer time. 相似文献
9.
Markus Arnold Elisabeth Lang Paola Modicano Rosi Bissinger Caterina Faggio Majed Abed Florian Lang 《Basic & clinical pharmacology & toxicology》2014,114(5):421-426
Nitazoxanide, a drug effective against a variety of pathogens, triggers apoptosis and is thus considered to be employed against malignancy. Similar to nucleated cells, erythrocytes may undergo an apoptosis‐like suicidal cell death or eryptosis. Hallmarks of eryptosis include cell shrinkage and phospholipid scrambling of the cell membrane with translocation of phosphatidylserine to the erythrocyte surface. Stimulators of eryptosis include increase in cytosolic Ca2+‐activity ([Ca2+]i). The Ca2+‐sensitivity of eryptosis is increased by ceramide. This study explored whether nitazoxanide triggers eryptosis. [Ca2+]i was estimated from Fluo3‐fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin‐V‐binding, ceramide abundance utilizing fluorescent antibodies and haemolysis from haemoglobin release. A 48‐hr exposure to nitazoxanide (1–50 μg/ml) did not significantly modify [Ca2+]i but significantly increased ceramide formation, decreased forward scatter (≥10 μg/ml), increased the percentage of annexin‐V‐binding erythrocytes (≥10 μg/ml) and, at higher concentrations (≥20 μg/ml), stimulated haemolysis. The stimulation of annexin‐V‐binding was significantly blunted in the absence of calcium. Nitazoxanide thus stimulates eryptosis, an effect in part due to ceramide formation. 相似文献
10.
The effect of 8-methoxypsoralen (8-MOP) in the dark on proliferation of phytohaemagglutinin-stimulated human lymphocytes has been examined, using total blood leucocytes, the lymphocyte fraction and the T-lymphocyte subpopulation. 8-MOP (1 microgram mL-1) increased [3H]TdR incorporation and caused a rise in the blastic and mitotic index in all experimental cultures. The lymphocyte proliferation in these experiments was effected by a comitogenic effect of 8-MOP on T-lymphocytes. 相似文献
11.
Majed Abed Kousi AL. Zoubi Michael Theurer Florian Lang 《Basic & clinical pharmacology & toxicology》2013,113(5):347-352
Dermaseptin, an antimicrobial peptide participating in the host defence against pathogens, interacts with the membrane of target cells, leading to membrane permeabilization and eventual cell lysis. Dermaseptin has previously been shown to trigger haemolysis. Prior to haemolysis, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling leading to phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increase in cytosolic Ca2+ activity [(Ca2+)]i and formation of ceramide. This study explored whether dermaseptin modifies [Ca2+]i and elicits eryptosis. Cell volume has been estimated from forward scatter, phosphatidylserine exposure from annexin‐V binding, haemolysis from haemoglobin release, ceramide formation from binding of fluorescent antibodies and [Ca2+]i from Fluo3‐fluorescence. A 48‐hr exposure to dermaseptin (50 μM) was followed by a significant increase in [Ca2+]i, a significant increase ceramide abundance, a significant decrease in forward scatter and a significant increase in annexin‐V binding. The annexin‐V binding after dermaseptin treatment was significantly blunted but not abrogated in the nominal absence of extracellular Ca2+. Dermaseptin triggers eryptosis, an effect at least partially due to entry of extracellular Ca2+. 相似文献
12.
E Donath A Herrmann W T Coakley T Groth M Egger M Taeger 《Biochemical pharmacology》1987,36(4):481-487
The influence of the antivirus drugs amantadine and rimantadine and of the anionic analogue 1-adamantane-carboxylic acid on a range of properties of human erythrocyte membrane and of thrombocytes has been compared with the effect of the local anaesthetic tetracaine. At low antiviral drug concentrations the abilities of the drugs to induce erythrocyte shape change and suppress osmotic haemolysis were quantitatively proportional to their clinical potency (rimantadine more effective than amantadine at the same concentration). Rimantadine was also more effective than amantadine in suppressing influenza virus-erythrocyte fusion and viral induced haemolysis. The antiviral drug effects were qualitatively similar to those induced by tetracaine. At the quantitative level, tetracaine was more efficient than the antiviral drugs in inhibiting osmotic haemolysis, virus membrane fusion and platelet aggregation. In the absence of any specificity of the antiviral drug effects we argue for a lysosomotropic mode of drug action, i.e. that the drugs modify virus-membrane interactions by changing the endosomal or lysosomal pH. 相似文献
13.
5-Methoxypsoralen (5-MOP) is used in cosmetic suntan preparations to stimulate the production of skin pigments. Although its isomer 8-methoxypsoralen (8-MOP) has been shown to be genotoxic in numerous biological systems, 5-MOP has not been so extensively investigated, but it has recently been reported to be mutagenic and carcinogenic. We have studied the lethal effects of 5-MOP and near ultraviolet light (NUV) on repair-deficient Escherichia coli strains. After treatment with 5-MOP at concentrations above 2 μg/ml in combination with UV light survival of the repair-deficient strains was considerably reduced and strain WP100 uvrA? recA? was more sensitive than strain WP2 uvrA?. The effect was dependent on the time of irradiation and on the presence or absence of S-9 mix which inhibited the lethal activity of 5-MOP/NUV particularly when the NADP-generating system was included. These results support other indications that the use of 5-MOP in cosmetic preparations should be controlled. 相似文献
14.
In this study, the potential toxicity of non-functionalized polystyrene nanoparticles (PS-NPs) in human erythrocytes has been assessed. The effect of PS-NPs with different diameters (∼30 nm, ∼45 nm, ∼70 nm) on fluidity of erythrocytes membrane, red blood cells shape, as well as haemolysis of these cells has been investigated. Erythrocytes were incubated for 24 h with non-functionalized PS-NPs in concentrations ranging from 0.001 to 200 μg/mL in order to study haemolysis and from 0.001 to 10 μg/mL to determine other parameters. Fluidity was estimated by electron paramagnetic resonance (EPR) and the fluorimetric method. It has been shown that PS-NPs induced haemolysis, caused changes in the fluidity of red blood cells membrane, and altered their shape. Non-functionalized PS-NPs increased the membrane stiffness in the hydrophobic region of hydrocarbon chains of fatty acids. The observed changes in haemolysis and morphology were dependent on the size of the nanoparticles. The smallest PS-NPs of ∼30 nm (with the smallest absolute value of the negative zeta potential −29.68 mV) induced the greatest haemolysis, while the largest PS-NPs of ∼70 nm (with the highest absolute value of the negative zeta potential −42.00 mV) caused the greatest changes in erythrocyte shape and stomatocytes formation. 相似文献
15.
The haemolytic effect of verapamil on red blood cells (RBCs) exposed to varying osmolarity was investigated. The experimental approach used a modified red cell haemolysis assay with concentrations of verapamil ranging from 50-1500 microM compared to drug free controls. The time-course of haemolytic effects was also investigated. We also briefly determined the haemolytic effects of verapamil in Ca2+-free conditions (with added EGTA). In conditions representing decreasing osmolarity (dilution from 140-0 mM NaCl) there was a significant increase in erythrocyte haemolysis that was also dependent on verapamil concentration (ANOVA, p<0.05). The red cells also showed a significantly increased rate of haemolysis over 5 h with increasing verapamil concentration (ANOVA, p<0.05). The degree of RBC hypotonic haemolysis was significantly increased in a Ca2+-free medium (+EGTA) compared to normal saline and this effect was exacerbated by additions of verapamil (ANOVA, p<0.05). Overall the data suggested that verapamil can cause haemolysis of RBCs in a predictable time- and concentration-dependent manner, and that verapamil increases the fragility of the erythrocytes further during hypotonic osmotic stress and Ca2+-free conditions. The mechanism of verapamil-dependent haemolysis could be directly related to the observed biphasic concentration-effect and could consequently involve several ion transport pathways. 相似文献
16.
BACKGROUND: It has been shown that cytochrome P450 enzymes (CYPs) and acetyltransferase can be used as biomarkers of carcinogen-DNA adduct levels and human cancer susceptibility. The gastrointestinal tract is the portal of entry of foreign compounds and presents xenobiotic metabolizing N-acetyltransferase (NAT) and CYPs activities. 5-Methoxypsoralen (5-MOP) has been used in combination with UV radiation in skin photochemotherapy for decades. A number of studies have demonstrated that 5-MOP is inhibitory towards mouse and human CYP isoforms, but investigations on the direct effects on NAT activity in laboratory animals and human cancer cells are limited. The main objective of this study was to document the effects of 5-MOP on the modulation of NAT activities in the stomach and colon of rats and human stomach and colon tumor cell lines. MATERIALS AND METHODS: N-Acetylation of 2-aminofluorene (AF) to 2-acetylaminofluorene (AAF) by NAT in the stomach and colon of Sprague-Dawley (SD) rats and in human stomach (SC-M1) and colon (COLO 205) tumor cell lines was investigated. RESULTS: The data show that the metabolic activity of NAT in the rat colon was higher than that in the rat stomach, and the further metabolism of AAF was slower in the stomach than in the colon. 5-MOP increased the activity of NATand also increased the further metabolism of AAF at 24 h in the rat stomach. In the rat colon, no statistically significant changes caused by 5-MOP were observed in NAT activity, but 5-MOP increased the further metabolism of AAF at 24 to 72 h. 5-MOP decreased the activity of NAT only at 72-h incubation in SC-M1 cells. In COLO 205 cells, however, 5-MOP decreased the activity of NAT between 24 h and 72 h. The optimal concentrations of 5-MOP to induce decreased NAT activity in SC-M1 cells were 0.05 mM to 25 mM. In COLO 205 cells, the data indicate that the higher the concentrations of 5-MOP, the higher the acetylation of AF; a promotion effect of NAT activity occured at a higher dose (50 mM) of 5-MOP and an inhibition effect occured at lower doses (0.05-0.5 mM) of 5-MOP, while concentrations of 5-25 mM of 5-MOP showed no significant difference compared with the control regimen. CONCLUSION: The metabolic activity of NAT in the rat colon was higher than that in the rat stomach, and the results also showed a high degree of correspondence with SC-M1 cells and COLO 205 cells. 5-MOP more efficiently inhibited NAT activity in human stomach and colon tumor cell lines than in the stomach and colon of rats. 相似文献
17.
《Toxicology in vitro》2010,24(4):1203-1207
To approach the real haemolytic process of jellyfish toxins, both in vitro and in vivo haemolysis of tentacle-only extract (TOE) from jellyfish Cyanea capillata has been studied. Dose–response curves of the haemolytic activity of TOE in vitro were sigmoid shaped in both erythrocyte suspension and diluted whole blood, with the former more sensitive to TOE. The in vivo haemolysis increased sharply in the first 10 min and was followed by a gradual increase in the following 3 h, with increasing blood potassium and lactic acid accordingly. SC5b-9 complexes were significantly up-regulated in vitro, but not in vivo. These results showed that the haemolysis of TOE in diluted whole blood and in vivo is not totally consistent with that in the erythrocyte suspension, and blood plasma might play a protective role against haemolysis. Thus we suggested that erythrocyte suspension can be used to test the damage of toxin on erythrocyte membrane, while the diluted whole blood may be more suitable to test the haemolysis of toxins. 相似文献
18.
ANNIE ABELLA CHERIF MESSAOUDI DENIS LAURENT DIDIER MAROT JACQUELINE CHALAS JOCELYNE BREUX CATHERINE CLAISE & ALBERT LINDENBAUM 《British journal of clinical pharmacology》1996,42(6):737-741
1Since oxygen free radicals are directly involved in a variety of pathologies such as atherosclerosis, diabetes mellitus, inflammation and/or when a deficit of defences of the organism against radicals occurs, we developed a suitable and simple method to determine both the erythrocyte sensitivity to an oxidative stress and plasma antioxidant protective capacity.
2This test is based on the introduction at 37° C of a radical initiator, 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH), within an erythrocyte suspension leading to a membrane alteration and ultimately to haemolysis. The latter can be quantified by determining the lacticodeshydrogenase activity released in the medium. The erythrocyte sensitivity to haemolysis and the volume of plasma inhibiting 50% of the haemolysis were determined.
3Intra-assay CVs were 1.9 % for erythrocyte sensitivity to oxidative stress and 3.4% for inhibitory 50% plasma volume. Inter-assay CVs for both erythrocyte sensitivity and inhibitory 50% plasma volume were 4%.
4The reliability of this method was assessed and applied to test the protective effect of vitamin E, a well known antioxidant agent, in six healthy volunteers. Two weeks after daily administration of 500 mg of vitamin E, the mean plasma vitamin E concentration increased by 41% from 10.7±2.0 mg l−1 before treatment (P<0.05). As the vitamin E concentration increased, the mean inhibitory 50% plasma volume and the percentage of haemolysed erythrocytes decreased respectively by 29% from 3.35±0.5 μl (P<0.05) and 18% from 71.5±3.8% (P<0.05). No significative variation of these parameters was observed in six adult men without vitamin E supplementation.
5Thus, this global and simple test permits an antioxidant status evaluation of a patient. It can be applied to various pathologies and allows the potency of new antioxidant molecules to be evaluated. 相似文献
19.
George I. Malinin William J. Vornberger Francis J. Hornicek Theodore I. Malinin 《Archives of toxicology》1996,70(3-4):182-188
The 72-h dark interaction of cultured osteoblasts with 0.5 – 1.0 μg/ml 8-methoxypsoralen (8-MOP) resulted in the accumulation
of cytoplasmic lipid droplets (steatosis) in target cells. These methanol-extractable lipid droplets and 8-MOP, however, had
no microscopically detectable effect on the organization of α-actin and β-tubulin-containing filaments. On the ultrastructural
level, psoralen effects ranged from negligible to unambiguous structural alterations of target cells. The latter consisted
of blebbing, segmental deletions of the nuclear envelope, and structural unraveling of nucleoli. Moreover, the dilatation
of the rough endoplasmic reticulum, the decrease in the number of ribosomes, and the extensive vacuolation of cytoplasm constituted
yet another hallmark of the 8-MOP effect in the absence of light. Whereas psoralen has induced a number of structural alterations
in some, but not in all osteoblasts, more than 95% of the target cells have, nonetheless, remained viable. Taken together,
our results suggest that the dark reaction of psoralen with osteoblasts results mainly in transient structural alterations
of affected cells.
Received: 19 April 1995 / Accepted: 21 August 1995 相似文献
20.
8-Methoxypsoralen (8-MOP), a naturally occurring compound, is a potent modulator of epidermal cell growth and differentiation in combination with ultraviolet light. However, there is little information on 8-MOP contribution to cell apoptosis alone. In the study, we evaluated 8-MOP, independently of its photoactivation, induced apoptosis in human hepatocellular carcinoma HepG2 cells. And we provide a molecular explanation linking 8-MOP to induce apoptosis. In HepG2 cells, treatment with 8-MOP induced the cell apoptosis in both dose-dependent and time-dependent manners. IC(50) values of 8-MOP were 8.775, 5.398μM for 48 and 72h, respectively. Further study showed that 8-MOP decreased the procaspase-3, procaspase-8, and procaspase-9, increased the ratio of Bax/Bcl-2 and decreased the survivin. Moreover, 8-MOP decreased differentiated embryonic chondrocyte gene1 (DEC1). Overexpression of DEC1 antagonized partially apoptosis induced by 8-MOP. And overexpression of DEC1 abolished the decrease of survivin and the activation of caspase-3 induced by 8-MOP partially. So, down regulation of DEC1 is involved in 8-MOP-induced apoptosis in HepG2 cells. Here, it is demonstrated that DEC1 possesses anti-apoptotic effects in 8-MOP-treated HepG2 cells. The findings provide more of a basis for 8-MOP as an anti-tumor agent in cancer therapy. 相似文献