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EPR study on the photosensitized generation of reactive oxygen species by actinomycin D

Science China Chemistry 2002年第5期45卷 449-454页

作者：潘景喜张素萍屠铁成韩镇辉蔡喜臣姚思德林念芸 Laboratory of Radiation Chemistry Shanghai Institute of Nuclear Research Chinese Academy of Sciences Shanghai 201800 China Institute of Plant Physiology Chinese Academy of Sciences Shanghai 200032 China

actinomycin D (AMD) is an anticancer antibiotic that can bind selectively to both double-stranded and single-stranded DNA, and this binding greatly enhances DNA photosensitization. Using electron paramagnetic resonance (EPR) in combination with spin trapping techniques, a systematic study was carried out on the reactive oxygen species generated in the photosensitization process of AMD. It was found that 1O2 and $O_2^{ - \cdot } $ are important reactive intermediates either in solution or in DNA complexes, and the generation of these species is in competition. This finding suggests that the photodynamic action of AMD proceeds via two pathways: energy transfer (type I mechanism) and electron transfer (type II mechanism). 1O2 is the main product formed via energy transfer reaction in solution while electron transfer between the excited states of AMD and DNA becomes the predominant pathway in DNA complexes.

关键词： actinomycin D, EPR, reactive oxygen species, photodynamic action.

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Combination Therapy of actinomycin D and Cisplatin Achieved Stronger Cytotoxicity via Increasing PUMA Expression on KB Cells

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中国药理学通报 2015年第B11期31卷 239-239页

作者： WANGLin XUHuan-li YANGSheng-qian DUGuan-hua Beijingkeylaboratoryofdrugtargetsresearchandnewdrugscreening theInstituteofMateriaMedicaPekingUnionMedicalCollege100055Chian DepartmentofPharmacology SchoolofBasicMedicinetheCapitalUniversityofMedicalSciences

Aim To study the synergistic effect and mechanism of actinomycin D to the anti-cancer activity of cispl- atin on KB cells. Methods Cytotoxicity of actinomycin D on KB cells was evaluated by MTT and LDH Assay. Apoptosis was detected by Flow cytometry （FCM）. Expression of p53, PUMA, Bax, Bcl-2 and Bcl-xl was detected by WB （Western blot） or IF （immunofluorescence staining）. The translocation of PUMA, Bax, Bcl-2 and Bcl-xl was detected by confocal microscope. PUMA knockdown was achieved by PUMA siRNA. Results actinomycin D synergistically enhanced the cytotoxicity of cisplatin on KB cells. Time-dependent increasing of PUMA and p53 in- duced by actinomycin D was accompanied by the translocation of PUMA and Bax/Bcl-xl in KB cells. Knockdown of PUMA effectively blocked the synergistic effect of actinomycin D to cisplatin. Conclusion actinomycin D effi- ciently enhanced the anti-cancer activity of cisplatin on KB cells. Up-regulation of PUMA by actinomycin D is like- ly responsible for the observed synergistic effect between the two drugs. Combination of actinomycin D and cisplatin may lead to an effective cancer treatment strategy.

关键词： actinomycin D cisplatin anti-cancer activity PUMA

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Effects of glucocorticoid dexamethasone on serum nitric oxide synthase activity and nitric oxide levels in a rat model of lung disease-induced brain injury

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Neural Regeneration Research 2011年第25期6卷 1971-1976页

作者： Huajun Li Ligang Jiang Meng Xia Haiping Li Fanhua Meng Wei Li Lifeng Liu Zhaohui Wang Department of Neurology Air Force General Hospital Beijing 100142 China Department of Neurobiology Affiliated Hospital of Beihua University Jilin 132011 Jilin Province China Department of Neurology Beijing Shijingshan Hospital Beijing 100043 China Medical School of Beihua University Jilin 132001 Jilin Province China

In this study, we investigated the effects of dexamethasone, pertussis toxin （a Gi protein inhibitor） and actinomycin （a transcription inhibitor） on serum nitric oxide synthase activity and nitric oxide content in a rat model of lung disease-induced brain injury. High-dose dexamethasone （13 mg/kg） and dexamethasone ＋ actinomycin reduced lung water content, increased serum nitric oxide synthase activity and nitric oxide content, diminished inflammatory cell infiltration in pulmonary alveolar interstitium, attenuated meningeal vascular hyperemia, reduced glial cell infiltration, and decreased cerebral edema. These results demonstrate that high-dose glucocorticoid treatment can reduce the severity of lung disease-induced brain injury by increasing nitric oxide synthase activity and nitric oxide levels.

关键词： glucocorticoid lung disease-induced brain injury nitric oxide nitric oxide synthase dexamethasone actinomycin neural regeneration

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Binding of Hoechst with nucleic acids using fluorescence spectroscopy

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Journal of Biophysical Chemistry 2011年第4期2卷 443-447页

作者： Nikolai Vekshin 不详

It has been shown that polarity of environment around Hoechst 33342 is almost unchanged while sorption of this fluorescent dye on a surface of the hairpin oligonucleotide HP1, t-RNA and DNA. At small concentrations, this dye, adsorbed on the surface of DNA, RNA or HP1, does not show any specificity to certain nucleotides. In the case of unwound sites of DNA or HP1, it can bind inside, but without the intercalation stacking with nucleotides. The energy transfer from nucleotide chromophores to Hoechst is absent due to their remoteness and also “bad” (non-stacking) orientation. The mutual fluorescence quenching of Hoechst by actinomycin D (AMD) and, vice versa, of 7-amino-actinomycin D (7AAMD) by Hoechst in DNA and HP1 is observed. It is due to dynamic deactivation and mutual replacing in binding sites.

关键词： Hoechst Fluorescence Quenching DNA t-RNA Oligonucleotide actinomycin

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