Molecular and cellular pharmacology最新文献_第7页

Compound-Induced Block of Ion Channel Pore Function: Inward-Rectifier Potassium Channels as a Model 化合物诱导的离子通道孔功能阻滞:以内向整流钾通道为模型

Molecular and cellular pharmacology Pub Date : 2009-12-28 DOI: 10.4255/MCPHARMACOL.09.29

Kazuharu Furutani, H. Hibino, A. Inanobe, Y. Kurachi

{"title":"Compound-Induced Block of Ion Channel Pore Function: Inward-Rectifier Potassium Channels as a Model","authors":"Kazuharu Furutani, H. Hibino, A. Inanobe, Y. Kurachi","doi":"10.4255/MCPHARMACOL.09.29","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.09.29","url":null,"abstract":"Small chemical compounds modulate ion channel functions. This is the reflection of ligand interactions with ion channels at their various sites. Many biophysical and biochemical researches have been performed on this subject and have provided important basic concepts on the structure-functional relationships of ion channels. Especially, ion channel blockers have been excellent tools for biophysical studies of ion channels and some of them are actually used for treating various diseases. The mechanisms underlying the blocking action of various chemical compounds, however, remain largely unknown at the atomic level, partly because of the promiscuous nature of the reaction. As one of the attempts to overcome the problem, we have adopted a novel approach combining molecular pharmacology and in silico analyses in the study of block of astroglial Kir4.1 channel by various antidepressants, including nortriptyline and fluoxetine. In molecular pharmacology experiments, we have demonstrated that Thr128 and Glu158 of Kir4.1 facing the central cavity play an important role in determining the sensitivities of the Kir channel to the antidepressants. On the other hand, we abstracted common sets of features from Kir4.1 channel blockers by the computer-aided technique that quantitatively correlates their chemical structures with IC 50 values for Kir4.1 channel current block. By combining these two lines of studies, we modeled the channel-drug interaction for Kir4.1-block, showing that the compound is accommodated between Thr128 and Glu158 within the central cavity of the channel. This combined approach may be useful to obtain some insights in the structure-function relationship of various ion channels and will shed light on the basic understandings of ion permeation and block.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"18 1","pages":"234-244"},"PeriodicalIF":0.0,"publicationDate":"2009-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84436916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Corrigendum to: Differentiation of cochlear neural progenitors with SV40 in vitro (Molecular and Cellular Pharmacology (2009) 1, (11-22)) SV40体外分化耳蜗神经祖细胞的研究(分子与细胞药理学，2009,1，(11-22))

Molecular and cellular pharmacology Pub Date : 2009-12-01 DOI: 10.4255/MCPHARMACOL.09.28

Jizhen Lin

引用次数: 0

Differentiation of cochlear neural progenitors with SV40 in vitro SV40体外诱导耳蜗神经祖细胞分化

Molecular and cellular pharmacology Pub Date : 2009-12-01 DOI: 10.4255/MCPHARMACOL.09.03

Ling Feng, Y. Hamajima, M. Komori, John C. Anderson, Dong Wang, T. Burns, C. Verfaillie, W. Low, Jizhen Lin

引用次数: 2

Targeting Chronic Pain with Epigenetic Drugs: Focus on mGlu2 Receptors 表观遗传药物靶向慢性疼痛:关注mGlu2受体

Molecular and cellular pharmacology Pub Date : 2009-08-10 DOI: 10.4255/MCPHARMACOL.09.23

S. Chiechio, M. Zammataro, R. Gereau, A. Copani, F. Nicoletti

{"title":"Targeting Chronic Pain with Epigenetic Drugs: Focus on mGlu2 Receptors","authors":"S. Chiechio, M. Zammataro, R. Gereau, A. Copani, F. Nicoletti","doi":"10.4255/MCPHARMACOL.09.23","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.09.23","url":null,"abstract":"Histone deacetylase (HDAC) enzymes regulate gene expression by affecting chromatin structure and/or the activity of transcription factors. We have recently demonstrated that histone deacetylase inhibitors (HDACIs) behave as epigenetic agents capable of inducing analgesia by up-regulating metabotropic glutamate type 2 (mGlu2) receptors. Specifically, the regulation of mGlu2 receptor expression appears to involve the acetylation of the NF- k B transcription factor. mGlu2 and mGlu3 receptors belong to class II metabotropic glutamate receptors. These receptors are coupled to G i/o proteins and play an important role in mediating antinociception in a variety of inflammatory and chronic pain models. We have shown that the HDACI-mediated mGlu2 receptor up-regulation occurs in the dorsal horn of the spinal cord and in the dorsal root ganglia, supporting a predominant role for mGlu2 receptors as mediators of analgesia in experimental animal models of chronic pain. We suggest that drugs that increase the expression of mGlu2 receptors, such as HDACIs or acetylating drugs (e.g. L-acetylcarnitine), may be effective in patients with chronic pain that are refractory to conventional analgesics.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"45 Suppl 3 1","pages":"194-199"},"PeriodicalIF":0.0,"publicationDate":"2009-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72678308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis. HIV Nef-M1在肿瘤诱导的脾脏和肝转移中对结直肠癌生长的影响

Molecular and cellular pharmacology Pub Date : 2009-08-05 DOI: 10.4255/mcpharmacol.09.10

Willie Harrington, Vincent Bond, Ming Bo Huang, Michael Powell, James Lillard, Upender Manne, Harvey Bumpers

{"title":"HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis.","authors":"Willie Harrington, Vincent Bond, Ming Bo Huang, Michael Powell, James Lillard, Upender Manne, Harvey Bumpers","doi":"10.4255/mcpharmacol.09.10","DOIUrl":"https://doi.org/10.4255/mcpharmacol.09.10","url":null,"abstract":"<p><p>CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1alpha, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis.</p>","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 2","pages":"85-91"},"PeriodicalIF":0.0,"publicationDate":"2009-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851221/pdf/nihms183448.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28915154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Human arylamine N-acetyltransferase 1 (NAT1) as a target of chemotherapeutic drugs in breast cancer: cisplatin as a model 人芳胺n -乙酰转移酶1 (NAT1)作为化疗药物在乳腺癌中的靶点:以顺铂为模型

Molecular and cellular pharmacology Pub Date : 2009-07-02 DOI: 10.4255/MCPHARMACOL.09.02

N. Ragunathan, J. Dairou, B. Pluvinage, Marta Martins, J. Dupret, F. Rodrigues-Lima

{"title":"Human arylamine N-acetyltransferase 1 (NAT1) as a target of chemotherapeutic drugs in breast cancer: cisplatin as a model","authors":"N. Ragunathan, J. Dairou, B. Pluvinage, Marta Martins, J. Dupret, F. Rodrigues-Lima","doi":"10.4255/MCPHARMACOL.09.02","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.09.02","url":null,"abstract":"Human arylamine N -acetyltransferase 1 (NAT1) is a phase II xenobiotic-metabolizing enzyme (XME) involved in the biotransformation of many aromatic amines and heterocyclic amines. This XME is known to play important roles in both the detoxication and/or bioactivation of numerous drugs and carcinogens. NAT1 is a polymorphic enzyme with a large tissue distribution. NAT1 polymorphisms and activity have been extensively studied because of its potential role in the biotransformation of important carcinogens. Several recent studies suggest that NAT1 may have a role in breast cancer progression. Indeed, this XME has been shown to affect the growth and drug resistance of breast cancer cells and appears to be a marker in human estrogen receptor positive breast cancer. Here we provide an overview of our recently published results indicating that NAT1 is a new target of the anticancer drug cisplatin in breast cancer cells. Moreover, these results are discussed in light of the data showing inhibition of human NAT1 and its mouse orthologue by natural and synthetic estrogens.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"89 1","pages":"7-10"},"PeriodicalIF":0.0,"publicationDate":"2009-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84245446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

PUMA Kills Stem Cells to Stall Cancer? 美洲狮杀死干细胞延缓癌症?

Molecular and cellular pharmacology Pub Date : 2009-06-01 DOI: 10.4255/mcpharmacol.09.14

Jian Yu

引用次数: 11

Molecular Determinant of Regioselective Hydroxylation of Docetaxel by CYP3A4 CYP3A4对多西紫杉醇区域选择性羟基化的分子决定因素

Molecular and cellular pharmacology Pub Date : 2009-05-24 DOI: 10.4255/MCPHARMACOL.09.09

B. Monsarrat, O. Thoison, J. Dubois, T. Cresteil

{"title":"Molecular Determinant of Regioselective Hydroxylation of Docetaxel by CYP3A4","authors":"B. Monsarrat, O. Thoison, J. Dubois, T. Cresteil","doi":"10.4255/MCPHARMACOL.09.09","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.09.09","url":null,"abstract":"The metabolism of taxanes by human liver microsomes is regioselective: the major metabolite of paclitaxel formed by CYP2C8 results from the hydroxylation on the taxane ring at C-6. Hydroxylations on the lateral chain at C-13 are catalyzed by CYP3A4 on either the tert -butyl of docetaxel or the C-3’ phenyl of paclitaxel. Furthermore, the presence of the acetyl group in position 10, has been shown to play an important role in determining the regioselective oxidation by CYP. The biotransformation of a series of docetaxel analogues by human liver microsomes and recombinant CYP expressed in HEK293 cells was examined by high-performance liquid chromatography/mass spectrometry. The formation of derivatives was lost when the tert -butyl of docetaxel was replaced by an ethyl group. Addition of an aliphatic chain at either position 7 or 10 led to the formation of oxidized metabolites, whereas addition at both 7 and 10 totally impaired the production of derivatives. Similarly, the insertion of a phenylbenzoyl group in position 10 prevented the biotransformation of the molecule. The site of hydroxylation could be clearly located on the aliphatic chain inserted in position 10, but remained on the tert -butyl at C-13 when the aliphatic chain was added in position 7. These reactions were catalyzed only by CYP3A4: recombinant CYP3A4 generated the same metabolites as liver microsomes did, whereas neither CYP3A5 nor 2C8 or 2C9 could form derivatives. In conclusion, the presence of substituents in position 10 of the docetaxel molecule plays a pivotal role in determining the site of oxidation by CYP3A4.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"221 1","pages":"76-84"},"PeriodicalIF":0.0,"publicationDate":"2009-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77448051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Novel Translational Research Concepts and Strategies in Radiation Oncology 放射肿瘤学新的转化研究概念和策略

Molecular and cellular pharmacology Pub Date : 2009-05-24 DOI: 10.4255/MCPHARMACOL.09.13

Seema Gupta, P. Goyal, Mansoor M Ahmed

{"title":"Novel Translational Research Concepts and Strategies in Radiation Oncology","authors":"Seema Gupta, P. Goyal, Mansoor M Ahmed","doi":"10.4255/MCPHARMACOL.09.13","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.09.13","url":null,"abstract":"The discovery of X-rays by Roentgen in 1895 and the discovery of radiations emitted from Uranium compounds by Becquerel led to the establishment of the field of Radiation Sciences. When Radiation Sciences utilized the knowledge in the field of Physics, Chemistry, Biology and Medicine, newer fields were established such as Radiation Oncology, -Chemistry, -Biology, -Protection, Physics, Radiology and Nuclear Medicine. Fields of Radiation Oncology and Radiation Biology have gained significant strides by embracing the modern concepts in molecular biology and physics of imaging. To discuss the recent trends and advances in these fields, Indian Society for Radiation Biology organized an “International Conference on Radiation Biology and Translational Research in Radiation Oncology (ICRB-TRRO)” in Jaipur, India during November 10-12, 2008. The primary theme of this international meeting was to focus on the translational research perspectives in radiation oncology using radiation biology findings as a reservoir of ideas. The second major theme was to focus on research initiatives and recent perspectives in radiation protection. A common dynamic theme constantly interacted with the primary and secondary themes was an influx of extensive discussion on the scientific utility and validity of novel agents obtained from different traditional systems of Indian medicine and herbal plant extracts that can be potent radio-sensitizers as well as potent radio-protectors (as countermeasure agents). Overall, four major thrust areas of the conference such as Radiation-induced signaling networks, novel therapeutics for cancer,","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"54 1","pages":"103-111"},"PeriodicalIF":0.0,"publicationDate":"2009-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80447112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Chemotherapeutics of neglected waterborne parasites: current status and future perspectives. 被忽视的水传播寄生虫的化疗:现状和未来展望。

Molecular and cellular pharmacology Pub Date : 2009-05-24 DOI: 10.4255/MCPHARMACOL.09.12

R. Chakrabarti, D. Chakrabarti

引用次数: 2