共查询到20条相似文献,搜索用时 31 毫秒
1.
Cutaneous protection against ultraviolet B (UVB) radiation damage by endogenous glutathione (GSH) was evaluated in the epidermis of the hairless mouse by measuring the influence of GSH depletion on sunburn cell (SBC) formation. Cellular GSH exerts antioxidant effects and recent studies have suggested a role for oxygen radicals in the production of SBC. Hairless mice (Skh/h 1) received oral treatment with buthionine S,R-sulfoximine (BSO), an irreversible inhibitor of gamma-glutamylcysteine synthetase, to deplete cutaneous GSH; 4 d later their ears were exposed to UVB radiation. BSO treatment significantly reduced GSH levels in the epidermis to 10-15% of control levels. Twenty-four hours after UVB exposure, SBC counts in the ears of animals with and without BSO treatment were measured, and those exposed to UVB were found to have increased. Greater numbers of SBC were found in the ears of BSO-treated mice exposed to 15 or 20 mJ/cm2 UVB, than in non-BSO-treated mice exposed to the same UVB doses. At higher UVB doses, there were no statistically significant differences between the groups. The results show that endogenous GSH provides the epidermis with measurable protection against injury by low or moderate UVB doses. 相似文献
2.
The cytotoxic and growth-inhibitory effect of levodopa methylester (LDME) in murine B16BL6 (BL6) melanoma cells after glutathione (GSH) depletion was studied in vitro. Pretreatment of BL6 cells with 50 microM buthionine sulfoximine (BSO) depleted GSH content by nearly 90% and enhanced the growth-inhibitory effect of even a minimally cytotoxic concentration of LDME. Radiothymidine incorporation into BL6 cells significantly increased compared to untreated controls during the first 4 h of exposure to 0.2 mM LDME. However, pretreatment with BSO prevented this LDME-induced increase in radiothymidine incorporation. Because the percentage of cells in S-phase of the cell cycle was not altered, these results suggest that BSO exposure may be inhibiting unscheduled DNA synthesis, which could contribute to the cytotoxic effects of LDME. In addition, spectrophotometric studies indicated that in a cell-free system, GSH scavenged dopaquinone produced by the tyrosinase-mediated oxidation of LDME, presumably by formation of glutathionyldopa. Thus, enhancement of LDME cytotoxicity by BSO may also involve depleting the amount of GSH available for the nucleophilic addition to the quinone. 相似文献
3.
Wróbel A Seltmann H Fimmel S Müller-Decker K Tsukada M Bogdanoff B Mandt N Blume-Peytavi U Orfanos CE Zouboulis CC 《The Journal of investigative dermatology》2003,120(2):175-181
Increased cell volume, accumulation of lipid droplets in the cytoplasm, and nuclear degeneration are phenomena indicating terminal differentiation of human sebocytes followed by holocrine secretion and cell death. The molecular pathways of natural and induced sebocyte elimination are still unknown, however. In this study, SZ95 sebocytes were found to exhibit DNA fragmentation after a 6 h culture followed by increased lactate dehydrogenase release after 24 h, indicating cell damage. With the help of morphologic studies and using Oil Red detection of cellular lipids, cell enlargement, accumulation of lipid droplets in the cytoplasm, and nuclear fragmentation could be observed under treatment with arachidonic acid. Staurosporine, a potent inhibitor of phospholipid Ca2+-dependent protein kinase, increased externalized phosphatidylserine levels on SZ95 sebocytes, detected by annexin V/propidium iodide flow cytometry, as early as after 1 h, whereas dose-dependent reduction of bcl-2 mRNA and protein expression, enhanced DNA fragmentation, and increased caspase 3 levels, detected by caspase 3 inhibitor/propidium iodide flow cytometry, were found after 6 h of treatment. SZ95 sebocyte death was detected as early as after 6 h of SZ95 sebocyte treatment with high staurosporine concentrations (10(-6)-10(-5) M). 5Alpha-dihydrotestosterone (10(-8)-10(-5) M) did not affect externalized phosphatidylserine levels and DNA fragmentation in SZ95 sebocytes but slightly decreased lactate dehydrogenase cell release. Neither acitretin nor 13-cis retinoic acid (10(-8)-10(-5) M) affected externalized phosphatidylserine levels, DNA fragmentation, and lactate dehydrogenase cell release, despite the increased caspase 3 levels under treatment with 13-cis retinoic acid. The combined staurosporine and 13-cis retinoic acid treatment enhanced DNA fragmentation in SZ95 sebocytes to the same magnitude as in cells only treated with staurosporine. In conclusion, SZ95 sebocytes in vitro undergo apoptosis, which can be enhanced by the terminal differentiation inductor arachidonic acid or by staurosporine and leads to cell death. 5Alpha-dihydrotestosterone inhibits SZ95 sebocyte death without involving apoptotic pathways, and retinoids did not affect the programmed death of human sebocytes. The latter result fits well with the currently reported inability of normal skin cells to undergo apoptosis after treatment with retinoids, in contrast to their malignant counterparts. 相似文献
4.
J.L. BOLOGNIA S.A. SODI M.P. OSBER J.M. PAWELEK 《The British journal of dermatology》1995,133(3):349-357
Glutathione (GSH) performs several important biological functions, including quenching of reactive oxygen species, and protection of cells from toxic compounds such as quinones. The first step in the synthesis of GSH is catalysed by γ-glutamylcysteine synthetase, an enzyme which is inhibited by cystamine and buthionine sulfoximine (BSO). In this study, we examined the possibility that the effect of hydroquinone (HQ) on pigmentation could be potentiated by inhibiting the production of GSH. In vitro studies using melanoma cell lines demonstrated that both cystamine and BSO could potentiate the inhibitory effects of HQ on tyrosinase activity and melanin content. A synergistic decrease in hair pigmentation was observed when a combination of HQ (2 or 4%) and BSO (5%) was applied to the dorsal skin of C57BL mice. In black hairless guinea-pigs, the application of HQ plus either BSO or cystamine resulted in a significant decrease in epidermal pigmentation when compared with any of the agents alone. The possibility exists that in the future a combination of HQ plus cystamine or BSO could be used to treat disorders such as melasma and post-Inflammatory hyperpigmentation. 相似文献
5.
Effects of cholera toxin on proliferation of cultured human keratinocytes in relation to intracellular cyclic AMP levels 总被引:2,自引:0,他引:2
In the culture of epidermal keratinocytes, the cellular growth rate is reported to be accelerated by cholera toxin. The mechanism by which cholera toxin exerts biological effects is thought to result from changes in intracellular cyclic AMP concentrations. But in many reports cyclic AMP elevating agents appeared to inhibit growth of keratinocytes in culture. This study was done to clarify the discrepancy of this problem. Determination of cyclic AMP revealed that cholera toxin over a range of 10-14-10-8 M increased the intracellular concentration of cyclic AMP of cultured keratinocytes about 100-fold over the controls after incubation for 6 hr. When a small number (10(5)) of cells were inoculated in a 60 X 15 mm culture dish, cholera toxin strongly stimulated colony growth. When a relatively larger number (8 X 10(5)) of cells were inoculated in a dish, cholera toxin moderately accelerated cell division, and increased DNA and protein levels of the culture during early days of cultivation. But after about 20 days, of cultivation when the culture reached confluence, cholera toxin decreased both DNA and protein content in a culture dish. The cultures were pulse labeled with 3H-thyrmidine at 12 and 24 hr after the addition of 10-10 M cholera toxin, and its uptake into DNA was determined. In the early days of cultivation the uptake of 3H-thymidine increased after treatment with cholera toxin. But in the late days of cultivation, cholera toxin decreased the rate of 3H-thymidine incorporation into DNA. These results indicated that cholera toxin-cyclic AMP has effects on the proliferation of keratinocytes in culture biphasically according to cellular concentrations in culture. 相似文献
6.
7.
Clinical evidence exists which suggests that normal pigment cell (melanocyte) function is subject to hormonal influences, but the nature of these interactions at a cellular level is poorly understood. We have investigated the effects of the vitamin D-derived secosteroid hormone 1 alpha-25, dihydroxyvitamin D3 (1,25(OH)2D3), the pituitary-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH), and the sex steroid beta-estradiol on melanocytes cultured from normal human foreskin. Human melanocytes specifically internalized 1,25(OH)2D3 with high affinity (Kd 0.5-0.8 nM). Incubation with 1,25(OH)2D3 (10(-9) M) for 48 h resulted in a 100% increase in 25-hydroxyvitamin D3-24-hydroxylase activity and a 50% increase in tyrosinase activity. There was no significant effect of 1,25(OH)2D3 on intracellular cyclic adenosine monophosphate (cAMP). In contrast to 1,25(OH)2D3, alpha-MSH at a concentration of 5 X 10(-7) M caused a sevenfold increase in intracellular cAMP after 12 min but only a modest increase (less than 20%) in melanocyte tyrosinase activity after 48 h. Incubation with beta-estradiol for 24 h caused a dose-dependent increase in tyrosinase activity. The maximal response varied from 145%-213% of basal activity depending on the donor source. These results indicate that melanocytes from normal human foreskin in culture have the capacity to respond directly to several hormones. They also suggest that these cells form a useful model to study the effect of various hormones on pigment cell function. 相似文献
8.
A method to obtain high-density primary cultures of adult and neonatal human melanocytes is described. Keratinocytes and melanocytes are coisolated from split-thickness sections fo neonatal foreskin obtained after circumcision, or from adult facial skin removed for cosmetic correction. Cells are released by trypsin and are plated in McCoy's 5A medium containing cholera enterotoxin (1 X 10(-9) M) and isobutylmethylxanthine (3.3 X 10(-5) M) to enhance melanocyte and keratinocyte multiplication. Keratinocytes and melanocytes are allowed to grow for 1 week. To remove associated keratinocytes, cells are exposed to 5-fluorouracil (5-FU) (1.92 X 10(-5), 3.84 X 10(-5), 1.92 X 10(-4) M). In the presence of low concentrations of 5-FU, keratinocytes are selectively destroyed within 3 weeks, while melanocytes continue to multiply and to form pigment. The differential effect of 5-FU on the multiplication of keratinocytes and melanocytes provides a simple method for obtaining cultures of melanocytes free from other nondendritic cell types present in the epidermis. 相似文献
9.
The effect of DOPA and glutathione (GSH) on enzyme systems for 5-S-cysteinyl-DOPA (5SCD) genesis in murine melanoma cells cultured in tyrosine- and cystine-free medium were studied. DOPA at its optimum concentration (10(-5) M) when added alone did not alter tyrosinase, glutathione-S-transferase or gamma-glutamyl transpeptidase activities. In the presence of GSH at its optimum concentration (10(-5) M), DOPA loading did not cause any significant changes in tyrosinase or glutathione-S-transferase (GST) activities. This indicates that the higher 5SCD levels observed in the medium because of DOPA loading in the GSH dependent system results from increased substrate availability rather than the increased enzyme activity. An acute drop in 5SCD at DOPA concentrations above 10(-5) M observed in the GSH dependent system may be due to the inhibition of tyrosinase at high substrate concentrations (10(-4) M). Conversely, in the presence of DOPA, when GSH was increased, the resultant higher production of 5SCD could be explained by the increased activity of GST. When added alone, GSH (10(-5) M) caused a significant increase in GST (approximately 125%) and gamma-GTP (approximately 50%) activities. A drop in 5SCD in the medium when GSH was added beyond its optimum concentration (10(-5) M) in the DOPA-dependent system could be due to competitive inhibition of gamma-GTP by GSH. The data demonstrate that 5SCD genesis may be enhanced due to the accumulation of cytotoxic melanin precursors such as DOPA/DOPA quinone. The relative quantities of GSH at the sites of DOPA quinone formation and the levels of its metabolising enzymes can influence the type of product formed.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
10.
The incorporation of precursor 14C-myoinositol into the three cellular inositol phospholipids (PtdIns, PtdInsP, and PtdInsP2) of cultured, rapidly proliferating keratinocytes is significantly enhanced by the exogenous addition of a high concentration (1 X 10(-7) M) of all-trans retinoic acid or its analog 13-Cis analog, whereas a similar incubation with a low concentration (1 X 10(-10) M) of the same retinoid resulted in an insignificant incorporation of the radio-precursor into the three inositol phospholipids. Incorporation was most marked into the more phosphorylated PtdIns4P and PtdIns4,5P2. These results indicate that retinoic acid affects the biosynthesis of the inositol phospholipids at high concentrations. In contrast, the hydrolysis of 14C-PtdIns4,5P2 and release of 14C-InsP3 from the prelabeled keratinocytes is markedly enhanced by a low physiologic concentration (1 X 10(-10) M) of retinoic acid or its 13-Cis analog. The hydrolysis is rapid, with an accompanying elevated transient release of 14C-InsP3. High concentration (1 X 10(-5) M), on the other hand, supresses 14C-InsP3 release. These results taken together underscore a bifunctional, dose-dependent effect of both the all-trans-RA and its 13-Cis analog on the synthesis and hydrolysis of keratinocyte PtdIns4,5P2. Furthermore, the results suggest that at low physiologic concentrations, these retinoids may function as agonists to perturb the membrane resulting in induced rapid hydrolysis of cellular PtdIns4,5P2, which is coupled to a "transient" generation of InsP3 (an intracellular second messenger). The rapid formation of this putative "second messenger" may in turn play a role in the cellular proliferative or differentiating biochemical events in the murine keratinocytes. 相似文献
11.
Biochemical studies on a novel vanadate- and molybdate-sensitive acid phosphatase from human epidermis 总被引:1,自引:0,他引:1
P L M?kinen 《The Journal of investigative dermatology》1985,85(2):118-124
A novel vanadate- and molybdate-sensitive human skin epidermal acid phosphatase was purified and characterized. The enzyme was extracted from epidermal sheets with a 0.1% Triton X-100 solution buffered at pH 7.0. The purification procedure consisted of molecular permeation chromatography on Sephadex G-200 followed by chromatography on hydroxylapatite using an ammonium sulfate gradient. The molecular weight of the enzyme was 82,000 and the isoelectric point was at pH 5.6. At the optimum pH (5.1) the enzyme hydrolyzed most rapidly 1-naphthyl phosphate (Km = 0.28 mM) and 4-nitrophenyl phosphate (Km = 0.28 mM). In general, the best substrates had an aromatic leaving group. Fluoride (Ki = 39 microM; noncompetitive) and phosphate (competitive) inhibited by binding to different binding sites of the enzyme. The most potent inhibitors were vanadate (Ki = 1.9 X 10(-6)M), tungstate (Ki = 1.4 X 10(-7)M), and molybdate (Ki = 2.0 X 10(-9)M). Chemical modification and kinetic experiments suggested that the activity of the enzyme is based on imidazole, tyrosyl, and carboxyl groups. Benzoyl peroxide was a relatively potent inhibitor (Ki = 5.0 X 10(-5)M; noncompetitive). This enzyme resembled the prostatic acid phosphatase with regard to substrate specificity, inhibition characteristics, and functional groups. 相似文献
12.
B.B. MICHIAK-MIKOLAJCZAK 《The British journal of dermatology》1984,111(3):309-314
A method has been developed to isolate a single rat eccrine sweat gland, together with the attached sweat duct, and to induce sweat secretion directly from the gland in vitro. Sweat production was induced using carbachol (2 X 10(-5) M to 3 X 10(-5) M) and methacholine (2 X 10(-5) M) in isolated plantar sweat glands maintained in a suitable environment (modified Krebs-Ringer bicarbonate at 38 degrees C containing 30% w/v fresh rat serum). The output of sweat was measured every 5 minutes for 85 minutes and the maximal final volume obtained with any one gland was 23 nl. Sweat production ceased on administration of appropriate concentrations of atropine (1 X 10(-5) M to 5 X 10(-5) M), withdrawal of calcium ions from the bathing fluid, and reduction of the medium temperature to 4 degrees C. 相似文献
13.
The role of specific retinoid receptors in sebocyte growth and differentiation in culture 总被引:4,自引:0,他引:4
Kim MJ Ciletti N Michel S Reichert U Rosenfield RL 《The Journal of investigative dermatology》2000,114(2):349-353
Retinoic acid derivatives (retinoids) exert their pleiotropic effects on cell development through specific nuclear receptors, the retinoic acid receptors and retinoid X receptors. Despite recent progress in understanding the cellular and molecular mechanisms of retinoid activity, it is unknown which of the retinoid receptor pathways are involved in the specific processes of sebocyte growth and development. In this study, we investigated the roles of specific retinoid receptors in sebocyte growth and differentiation, by testing the effects of selective retinoic acid receptor and retinoid X receptor ligands at concentrations between 10-10 M and 10-6 M in a primary rat preputial cell monolayer culture system. Cell growth was determined by number of cells and colonies, and cell differentiation by analysis of lipid-forming colonies. All-trans retinoic acid and selective retinoic acid receptor agonists (CD271 = adapalene, an RAR-beta,gamma agonist; CD2043 = retinoic acid receptor pan-agonist; and CD336 = Am580, an RAR-alpha agonist) caused significant decreases in numbers of cells, colonies, and lipid-forming colonies, but with an exception at high doses of all-trans retinoic acid (10-6 M), with which only a small number of colonies grew but they became twice as differentiated as controls (42.2 +/- 4.0% vs 22.6 +/- 2.7%, mean +/- SEM, lipid-forming colonies, p < 0.01). Furthermore, the RAR-beta,gamma antagonist CD2665 antagonized the suppressive effects of all-trans retinoic acid, adapalene, and CD2043 on both cell growth and differentiation. In contrast, the retinoid X receptor agonist CD2809 increased cell growth slightly and lipid-forming colonies dramatically in a clear dose-related manner to a maximum of 73.7% +/- 6.7% at 10-6 M (p < 0. 001). Our data suggest that retinoic acid receptors and retinoid X receptors differ in their roles in sebocyte growth and differentiation: (i) retinoic acid receptors, especially the beta and/or gamma subtypes, mediate both the antiproliferative and antidifferentiative effects of retinoids; (ii) retinoid X receptors mediate prominent differentiative and weak proliferative effects; (iii) the antiproliferative and antidifferentiative effects of all-trans retinoic acid are probably mediated by retinoic acid receptors, whereas its differentiative effect at high dose may be mediated by retinoid X receptors via all-trans retinoic acid metabolism to 9-cis retinoic acid, the natural ligand of retinoid X receptors. 相似文献
14.
Single cell suspensions of murine epidermal cells were studied for the generation of leukotrienes (LTs), using in vitro bioassays for chemotaxis, reverse-phase high-pressure liquid chromatography (HPLC), and radioimmunoassays (RIAs). A combination of arachidonic acid (AA) at 10(-3)-10(-4) M with the calcium ionophore A 23187 at 5 X 10(-6) M was the most potent stimulus, causing release of LTs within 10-30 min. Other stimuli, like the N-formyl-methionyl-leucyl-phenylalanine, at 10(-7) M and bradykinin at 10(-3) M, were less effective, and the tumor promotor phorbol-myristate-acetate (10(-5)-10(-8) M) caused no release at all. AA induced release at cytotoxic concentrations, but the other stimuli did not, and keratinocytes from different body regions were equally good sources of the LTs. In vivo or in vitro pretreatment of keratinocytes with UV radiation did not alter spontaneous or stimulated secretion of LTs, while pretreatment of cells with Ia, but not with Thy-1, monoclonal antibodies caused a moderate decrease of release. Analyses by HPLC indicated the release of 20-OH-LTB4 in addition to LTB4 in cell supernatants. Murine keratinocytes and epidermal dendritic cells serve therefore as a source of chemotactic leukotrienes after appropriate in vitro stimulation with agents that are known to play a role in cutaneous inflammation. 相似文献
15.
We have observed differential effects of the cytotoxicity of 5-fluorouracil (5-FU) on human skin melanocytes and malignant melanoma cells in vitro. In the absence of 5-FU the melanoma cells multiplied much more rapidly than the melanocytes. With a 7-day exposure of 5-FU (1.92 X 10(-5) to 3.84 X 10(-4) M) all the melanoma cells died by 5 W, while even two times longer exposure (a 14-day exposure) of 5-FU the melanocytes survived till 6 W and increased at the lower concentration. In the presence of 5-FU there was a different compensatory increase in [3H] thymidine incorporation between the two cell types. That is, compared with the large increase observed in the incorporation by the melanoma cells, a small increase in the incorporation by the melanocytes was observed. The reason for these differential effects of 5-FU may be the difference in the cell cycle and the post-injury cell renewal of the two cell types. 相似文献
16.
Buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis, showed variable growth-inhibitory activity in different tumor cell lines with a high degree of inhibitory activity against melanoma-derived cell lines. A correlation between BSO growth-inhibitory effects and cellular glutathione peroxidase activity was observed. In contrast, no correlation was demonstrated between the response to BSO and cellular tyrosinase, gamma-glutamylcysteine synthetase, glutathione transferase, gamma-glutamyl transpeptidase, or glutathione reductase activities. BSO enhanced 3,4-dihydroxybenzylamine (3,4-DHBA) (fourfold) and melphalan (threefold) in vitro cytotoxic activity as determined by inhibition of DNA synthesis in human melanoma cells and this enhancement was dependent on the duration of exposure to drug. BSO demonstrated in vivo antitumor activity in B16 melanoma-bearing mice prolonging survival by 29% and in combination with 3,4-DHBA resulted in a slight (48% versus 38%) increase in life span as compared to 3,4-DHBA alone. The combination of BSO and melphalan, however, increased the life span of B16 melanoma-bearing mice by 170%, as compared to melphalan alone (80%). These studies demonstrate a unique in vivo antimelanoma activity of BSO. 相似文献
17.
L Michel J M Mencia-Huerta J Benveniste L Dubertret 《The Journal of investigative dermatology》1987,88(6):675-681
Using an improved skin chamber technique, the consequences of prolonged contact of leukotriene B4 (LTB4) and platelet-activating factor (paf-acether) with human dermis were evaluated quantitatively and kinetically in vivo. Leukocyte chemotaxis, histoenzymologic alterations, and modifications in vascular permeability were studied in two sets of experiments. In a first set of experiments, the dose-effect relationship of LTB4 and paf-acether on leukocyte migration was studied. LTB4 (3 X 10(-8) M to 9 X 10(-7) M) in Hanks' balanced salt solution (HBSS) elicited an intense dose-dependent and time-dependent neutrophil migration. Paf-acether, at the same concentration range, induced a significant increase in cell migration only at 9 X 10(-7) M and when diluted in HBSS containing 0.25% serum albumin (HBSS-BSA). Histoenzymologic analysis demonstrated that LTB4 in vivo induced degranulation of most of the neutrophils migrating through the dermis. Paf-acether caused mild degranulation of neutrophils and induced the appearance of degranulated basophils in dermal vessels. A second set of experiments was designed to study simultaneously the modifications in vascular permeability and cell migration induced by LTB4 and paf-acether, with or without prostaglandin E2 (both at a concentration of 3 X 10(-7) M in HBSS). Since spontaneous protein diffusion in HBSS progressively declined up to a plateau reached after 20 h (1.2 +/- 0.15 mg of proteins/cm2/2 h), these experiments were carried out after a 20-h equilibration period. Leukotriene B4 induced a late and slight increase in vascular permeability. Paf-acether did so intensely and transiently. Prostaglandin E2 significantly enhanced protein diffusion and neutrophil migration induced by LTB4 and, to a lesser extent, by paf-acether. Interestingly, despite the reintroduction into the skin chambers of freshly prepared solutions containing the mediators, leukocyte migration and protein diffusion progressively decreased during the experiments. This suggests the local production of anti-inflammatory factors that inhibit local mediators and thus regulate the inflammatory response. 相似文献
18.
Dai X Yamasaki K Yang L Sayama K Shirakata Y Tokumara S Yahata Y Tohyama M Hashimoto K 《The Journal of investigative dermatology》2004,122(6):1356-1364
1,25-dihydroxyvitamin D3 (1,25[OH]2VD3) has an antiproliferative effect on keratinocyte growth, and its derivatives are used for the treatment of psoriasis. It was reported previously that 1,25[OH]2VD3 induced cell cycle arrest not only at the G0/G1 phase but also at the G2/M phase. However, the mechanism of 1,25[OH]2VD3-induced G2/M phase arrest in keratinocytes has not been fully understood. The addition of 10(-8) to 10(-6) M 1,25[OH]2VD3 to cultured normal human keratinocytes enhanced the expression of Myt1 mRNA preceding Wee1 mRNA; 10(-6) M 1,25[OH]2VD3 unregulated Myt1 mRNA from 6 h to 24 h and Wee1 mRNA from 12 to 48 h. Interestingly, the levels of phosphorylated Cdc2 were increased between 6 h and 48 h after 1,25[OH]2VD3 treatment, although the expression levels of Cdc2 mRNA and its protein production were reduced. 1,25[OH]2VD3 also decreased the expression of cyclin B1, which forms a complex with Cdc2. These data indicated that the increase of Myt1 and Wee1 induced the phosphorylation of Cdc2 leading to G2/M arrest. In conclusion, the induction of Cdc2 phosphorylation due to the increase of Wee1 and Myt1 as well as the reduction of Cdc2 and cyclin B1 are involved in 1,25[OH]2VD3-induced G2/M arrest of keratinocytes. 相似文献
19.
Biochemical modulation of angiogenesis in the chorioallantoic membrane of the chick embryo 总被引:15,自引:0,他引:15
A variety of substances potentially having effects on angiogenesis in the skin were assayed on the chorioallantoic membrane of the chicken embryo (CAM). Millipore filter discs alone and saturated with saline 0.9% (controls), keratinocyte-conditioned medium, lactic acid 10(-1) M, adenosine 10(-4) M, sodium fluoride 10(-4) M, dinitrophenol 10(-4) M, histamine 10(-4) M, 5-hydroxytryptamine 10(-4) M, acetylcholine 10(-4) M, prostaglandin E2 3 X 10(-4) M, prostaglandin F2 alpha 3 X 10(-4) M, arachidonic acid 10(-4) M, epidermal growth factor 5 X 10(-5) g/ml, human plasma fibronectin 10(-4) g/ml, acetylsalicylic acid 10(-3) M, and arachis oil were applied to the CAM and the vascular responses quantitated 4 days later. None of the agents with the exception of keratinocyte-conditioned medium stimulated new vessel growth as compared to the controls. However, arachis oil (p less than 0.001) and ADP (p less than 0.01) were associated with significantly decreased vascular responses relative to controls. The specimens incubated with saline, fibronectin, ADP, and arachis oil were examined histologically; with the exception of arachis oil all displayed ectodermal epithelial and mesenchymal hyperplasia of the membrane in association with increased vascularity. Almost no perceptible change was noted histologically with arachis oil. 相似文献
20.
ANITA REMITZ ARJA-LEENA KARINIEMI EERO LEHTONEN STIG NORDLING 《The British journal of dermatology》1989,120(4):525-531
The effects were studied of two antipsoriatic drugs, dithranol (anthralin) and butantrone on the proliferation of HeLa cells. Non-confluent monolayers of HeLa cells were treated with various concentrations (10(-5)-10(-8) M) of dithranol or butantrone for 45 min. The cells were then cultivated for up to 48 h and treated with 10 microM bromodeoxyuridine (BrdU) and 10 microM fluorodeoxyuridine for 30 min before harvesting. Both drugs at concentrations of 10(-6) and 10(-5) M inhibited the BrdU uptake of HeLa cells, but did not cause any significant change in the proportion of cells in S-phase. The inhibitory effect of dithranol on cell number was linear with concentration 24 h after incubation. The highest (10(-5) M) concentration of butantrone caused an abrupt decrease in cell number. 相似文献