• 한국미생물·생명공학회지
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• 제24권3호
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• pp.380-383
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• 1996

Adenosine deaminase inhibitor was extracted from culture broth of Streptomyces sp. strain V-8 with ethylacetate. The ethylacetate extract showed the characteristic UV absorption spectrum of actinomycins at 440-450 nm. The ethylacetate extract was compared with respect to inhibitory behavior against adenosine deaminase from calf intestinal mucosa with actinomycin D, -C complex and actinomycin V. The Ki values for actnomycin D, -C complex, and actinomycin V against adenosine deaminase were determined to be 9.9 $\times$ 10$^{-6}$ M, 9.6 $\times$ 10$^{-6}$ M and 9.3 $\times$ 10$^{-6}$ M, respectively. The Ki value for the ethylacetate extract of culture broth against adenosine deaminase was determined to be 5.7 $\times$ 10$^{-6}$ M. The kinetic parameters of actinomycin D, -C complex, -V and ethylacetate extract of culture broth for adenosine deaminase were as follows:I$_{50}$ = 1.5 $\times$ 10$^{-5}$ M (actinomycin D), 2.7 $\times$ 10$^{-5}$ M (actinomycin C complex), 3.5 $\times$ 10$^{-5}$ M (actinomycin V), 8.9 $\times$ 10$^{-6}$ M (ethylacetate extract of culture broth). The adenosine deaminase was inhibited noncompetitively by ethylacetate extract of culture broth as well as by actinomycin D, -C complex and actinomycin V.

• 생명과학회지
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• 제21권1호
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• pp.141-145
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• 2011

본 연구에서는 전사억제제(transcriptional inhibitor)로 알려진 actinomycin D가 전사조절인자(transcription factor)인 STAT의 인산화를 유도한다는 것을 확인하였다. Actinomycin D 처리 시 STAT1의 Tyr701, Ser727 인산화는 유도되지 않았지만 STAT3의 Tyr705 잔기의 인산화를 특이적으로 유도하는 것을 확인하였다. Actinomycin D에 의한 STAT3의 Tyr705 인산화 유도가 어떠한 기전을 통한 것인지 확인하기 위해서 관련 인자의 단백질 및 mRNA 발현을 확인한 결과 SOCS3의 단백질 및 mRNA 발현의 감소를 확인하였다. STAT3의 탈인산화를 유도한다고 알려진 tyrosine phosphatase인 SHP-1와 STAT의 upstream kinase인 JAK2의 인산화는 변화가 없었다. 또한 actinomycin D 뿐 아니라 다른 전사억제제인 DRB를 처리 하였을 경우에도 STAT3의 Tyr705 인산화가 유도되는 것을 확인하였다. 이상의 결과는 전사억제제에 의하여 특이적인 SOCS3 단백질 발현감소는 SOCS3의 하류의 target인 STAT3 인산화를 유도하였다.

• BMB Reports
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• 제36권3호
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• pp.305-311
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• 2003

A modified actinomycin D was prepared with a hydroxyl group that replaced the amino group at the chromophore 2-position, a substitution known to strongly reduce affinity for double-stranded DNA. Interactions of the modified drug on single-stranded DNAs of the defined sequence were investigated. Competition assays showed that 2-hydroxyactinomycin D has low affinity for two oligonucleotides that have high affinities ($K_a\;=\;5-10{\times}10^6\;M^{-1}$ oligomer) for 7-aminoactinomycin D and actinomycin D. Primer extension inhibition assays performed on several single-stranded DNA templates totaling around 1000 nt in length detected a single high affinity site for 2-hydroxyactinomycin D, while many high affinity binding sites of unmodified actinomycin D were found on the same templates. The sequence selectivity of 2-hydroxyactinomycin D binding is unusually high and approximates the selectivity of restriction endonucleases. Binding appears to require a complex structure, including residues well removed from the polymerase pause site.

• 한국동물학회지
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• 제26권4호
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• pp.225-233
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• 1983

哺乳動物의 排卵時 濾胞卵子의 成熟再開와 더불어 卵子를 緻密하게 둘러싸고 있는 卵子細胞들의 分散이 일어난다. 이 現象은 生殖巢刺戟호르몬의 促進을 받은 卵丘細胞들이 細胞間隔에 多量의 뮤코量을 分泌함으로써 이루어지는데 이 때 cAMP가 第二 傳達者로 作用을 한다고 알려져 있다. 본 實驗에서는 卵子-卵丘 複合體를 培養하면서 HCG (10 IU/ml)에 의해 誘導된 卵丘細胞의 分散에 puromycin과 actinomycin D가 미치는 영향을 調査한 바 다음과 같은 缺課를 얻었다. 1. Puromycin은 2 $\\mu$g/ml의 濃度에서 卵丘細胞의 分散을 현저히 抑制하였으며 이 效果는 可逆的이었다. 2. Puromycin의 分散抑制效果는 HCG의 刺戟기간 (3시간) 뿐 아니라 뮤코量의 合成時期 ($3\\sim18$시간)에서도 나타났다. 3. Actinomycin D는 0.025 $\\mu$g/ml의 濃度에서부터 卵丘細胞의 分散을 抑制하기 시작했다. 4. Actinomycin D의 分散抑制效果는 부분적인 可逆性을 나타내었으며 0.1 $\\mu$g/ml의 濃度에서는 非可逆的인 災害效果를 나타내었다. 위의 缺課로부터 HCG의 卵丘細胞 分散誘導過程에는 蛋白質 내지 RNA의 合成過程이 관여하는 것으로 測定되며 따라서 cAMP는 轉寫 내지 解讀水準에서 卵丘細胞의 分散을 調節하는 것 같다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3351-3354
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• 2015

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric age group. All patients with RMS regardless of their initial stage or group receive combination chemotherapy as 'standard therapy' consisting of vincristine, actinomycin-D and cyclophosphamide. Actinomycin-D was not readily available in Turkey at one time. Carboplatin was used instead in order to prevent delays in treatment. The aim of this report is to present the results of patients with rhabdomyosarcoma receiving carboplatin or actinomycin-D therapy. Materials and Methods: Twenty four patients with rhabdomyosarcoma treated between December 2000 and June 2011 were included in this retrospective study. The patients were treated according to International Rhabdomyosarcoma Study Group guidelines. Eleven patients were treated with actinomycin-D and 13 with carboplatin ($250mg/m^2/dose$ for 2 days). The two groups were then compared in terms of 2- and 5-year overall survival (OS) and hematological and non-hematological toxicities. Results: Age, sex, stage and the mean duration of follow-up were similar in both groups (p>0.05). Two- and five-year OS levels were 68.2% in the carboplatin group and 78.0% and 40.0%, respectively, in the actinomycin-D group. There was no statistical difference in the number of febrile episodes (p=0.86) and no other hematological and non-hematological adverse effects were recorded in both groups. Conclusions: The findings show that carboplatin can be used as an alternative drug in the primary treatment of rhabdomyosarcoma in the event that actinomycin-D is unavailable or not tolerated.

• Applied Microscopy
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• 제14권2호
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• pp.1-14
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• 1984

Chick embryos received a single injection of actinomycin D($0.1{\mu}g,\;0.05{\mu}g\;or\;0.1{\mu}g$) or puromycin($10.0{\mu}g,\;30.0{\mu}g\;or\;50.0{\mu}g$) into the yolk sac of Arbor acres chick embryos either prior to incubation or at certain periods of time (48, 96 and 144 hours) after incubation. After 10days of incubation, surviving embryos were investigated morphologically and biochemically. Embryos treated with actinomycin D or puromycin showed a high mortality when they were exposed prior to incubation and at 48 hours after incubation. Electron micrographs of chondrocytes in tarso-metatarsal of antibiotics (actinomycin D or puromycin) treated embryos showed the destruction of cytoplasm and nuclei when they were exposed prior to incubation. Endoplasmic reticulum was expanded and mitochondria were damaged in chondrocytes of surving embryos treated with low doses at 48 hours, 96 hours or 144 hours after incubation. The activities of enzymes such as lactate dehydrogenase, malate dehydrogenase and succinate dehydrogenase in embryos treated with actinomycin D or puromycin were much less than those of the saline treated group. Also, the amounts of DNA, RNA and protein were greatly decreased.

• Applied Microscopy
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• 제15권1호
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• pp.1-12
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• 1985

In this study, the pathway and date of migrating Primordial germ cells (PGCs) were observed light microscopically and ultrastructural changes of them during migration were observed by electron microscopic examination. For these purpose, alkaline phosphatase reactions were used for identifying the PGCs and acid phosphatase reactions were used for observing their degenerating activities. Also, effects of actinomycin D on the migration of PGCs were examined. According to these results, at the 9th gestation day, PGCs were observed in the endodermal cells of yolk sac, at the 11th gestation day, they were seen in the hindgut and then entered into the dorsal mesentery by the 13th gestation day. At the 14th gestation day, they were located in the genital ridges. When PGCs were located in the hindgut and genital ridges, the positive reactions of alkaline phosphatase were dominated, but acid phosphatase reactions were limited in all stage except they were in dorsal mesentery. However, these reactions were lessened in case of actinomycin D treatment. By electron microscopic examination, PGCs had pseudopodia, tail process, trailing cytoplasm and nuage as the ultrastructural characteristics. In addition, these morphological features were damaged by actinomycin D treatment.

• Journal of Plant Biology
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• 제25권1호
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• pp.3-8
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• 1982

As a part of the studies on the regulatory mechanism of gene expression by gibbrellic acid, the effects of $GA_3$ on the protein biosynthesis and phosphorylation in maize seedlings were investigated in the presence of actinomycin D. The activities of protein biosynthesis and phosphorylation in germinating seeds treated with $GA_3$ were greater than those of the control at the 3-day point after germination. It is assumed that the enhancement of protein biosynthesis by $GA_3$ in the presence of actinomycin D is due to the effects of $GA_3$ on the translational processes in which protein is produced from the mRNA synthesized previously.

• Applied Microscopy
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• 제13권1호
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• pp.71-84
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• 1983

This study was made to investigate the ultrastructural changes of the hepatocyte of the maternal liver, and fetal liver by Actinomycin D in Wistar rats at the stage of pregnancy. Peritoneal injection of Actinomycin D to rats carried out gestation day 7 to 9 at the level of $15{\mu}g(11.5{\mu}g/100g$ body wt.), $20{\mu}g(15.8{\mu}g/100g$ body wt.) on each day. Treated animals with saline only were used for controls. Animals were sacrificed on day 15 of gestation. On electron microscopic examination, the hepatocytes of maternal liver given Actinomycin D $15{\mu}g$/ml had evidence of serious cellular damage, for example, hypertrophy of rough endoplasmic reticulum, loss in nucleolar osmiophilia, swelling of Golgi apparatus and change of mitochondrial structure. Maternal liver given Actinomycin D $20{\mu}g/ml$ shown similar changes to that of the $15{\mu}g/ml$ treated animals. But mitochondria of this group were not changed than that of $15{\mu}g/ml$ treated group. In the hepatocytes of fetal liver, changes were more pronounced. The drug produced alteration in nuclei and cytoplasm. The rough endoplasmic reticulum was swollen and there were ribosomes detachement. In addition, damages of mitochondria, Golgi apparatus were detected.

• 한국수정란이식학회지
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• 제24권3호
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• pp.183-187
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• 2009

In this study, we aimed to determine whether the evaluated markers of cell death could be found at particular developmental stages of normal porcine in vitro fertilization (IVF) embryos. We investigated the characteristics of spontaneous and induced apoptosis during preimplantation development stages of porcine IVF embryos. In experiment 1, to induce apoptosis of porcine IVF embryos, porcine IVF embryos at 22h post insemination were treated at different concentration of actinomycin D (0, 5, 50 and 500 ng/ml in NCSU medium). Treated embryos were incubated at $39^{\circ}C$ in 5% $CO_2$, 5% $O_2$ for 8h, and then washed to NCSU medium and incubated until blastocyst (BL) stage. We examined cleavage rate at 2days and BL development rate at 7days after in vitro culture. A significantly lower rate of cleavage was found in the 500 ng/ml group compared to others (500 ng/ml vs. 0, 5, 50 ng/ml; 27.8 % vs. 50.0%, 41.2%, 35.9%), and BL formation rate in 500 ng/ml was lower than that of others (500 ng/ml vs. 0, 5, 50 ng/ml; 8.0% vs. 12.6%, 11.2%, 12.6%). In experiment 2, to evaluate apoptotic cells, we conducted TUNEL assay based on morphological assessment of nuclei and on detection of specific DNA degradation under fluorescence microscope. This result showed that apoptosis is a normal event during preimplantation development in control group (0 ng/ml actinomycin D). A high number of BL derived control group contained at least one apoptotic cell. Actinomycin D treated BLs responded to the presence of apoptotic inductor by significant decrease in the average number of blastomeres and increase in the incidence of apoptotic cell death. In 500 ng/ml group, the incidence of apoptosis increased at 4-cell stage and later. This result suggested that apoptosis is a process of normal embryonic development and actinomycin D is useful tool for the apoptosis study of porcine preimplantation embryos.