Molecular and cellular pharmacology最新文献_第9页

Novel Pharmacologic Approaches for the Management of Diabetic Retinopathy. 治疗糖尿病视网膜病变的新药理学方法。

Molecular and cellular pharmacology Pub Date : 2009-01-01 DOI: 10.4255/mcpharmacol.09.27

Jaclyn L Kovach, Stephen G Schwartz

引用次数: 3

Working together: Farnesyl transferase inhibitors and statins block protein prenylation. 协同工作:法尼基转移酶抑制剂和他汀类药物阻断蛋白戊烯酰化。

Molecular and cellular pharmacology Pub Date : 2009-01-01 DOI: 10.4255/mcpharmacol.09.01

Jonathan W Wojtkowiak, Richard A Gibbs, Raymond R Mattingly

引用次数: 23

Estrogen's Place in the Family of Synaptic Modulators. 雌激素在突触调节家族中的地位。

Molecular and cellular pharmacology Pub Date : 2009-01-01

Enikö A Kramár, Lulu Y Chen, Christopher S Rex, Christine M Gall, Gary Lynch

{"title":"Estrogen's Place in the Family of Synaptic Modulators.","authors":"Enikö A Kramár, Lulu Y Chen, Christopher S Rex, Christine M Gall, Gary Lynch","doi":"","DOIUrl":"","url":null,"abstract":"Estrogen, in addition to its genomic effects, triggers rapid synaptic changes in hippocampus and cortex. Here we summarize evidence that the acute actions of the steroid arise from actin signaling cascades centrally involved in long-term potentiation (LTP). A 10-min infusion of E2 reversibly increased fast EPSPs and promoted theta burst-induced LTP within adult hippocampal slices. The latter effect reflected a lowered threshold and an elevated ceiling for the potentiation effect. E2's actions on transmission and plasticity were completely blocked by latrunculin, a toxin that prevents actin polymerization. E2 also caused a reversible increase in spine concentrations of filamentous (F-) actin and markedly enhanced polymerization caused by theta burst stimulation (TBS). Estrogen activated the small GTPase RhoA, but not the related GTPase Rac, and phosphorylated (inactivated) synaptic cofilin, an actin severing protein targeted by RhoA. An inhibitor of RhoA kinase (ROCK) thoroughly suppressed the synaptic effects of E2. Collectively, these results indicate that E2 engages a RhoA >ROCK> cofilin> actin pathway also used by brain-derived neurotrophic factor and adenosine, and therefore belongs to a family of 'synaptic modulators' that regulate plasticity. Finally, we describe evidence that the acute signaling cascade is critical to the depression of LTP produced by ovariectomy.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 5","pages":"258-262"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858427/pdf/nihms183452.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28946923","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: 0

Sulindac Sulfide Differentially Induces Apoptosis in Smac-Proficient and -Deficient Human Colon Cancer Cells. Sulindac Sulfide诱导smac精通和缺乏的人结肠癌细胞凋亡的差异

Molecular and cellular pharmacology Pub Date : 2009-01-01 DOI: 10.4255/mcpharmacol.09.11

Jingxue Shi, Qin He, Jie An, Hong Sun, Ying Huang, M Saeed Sheikh

{"title":"Sulindac Sulfide Differentially Induces Apoptosis in Smac-Proficient and -Deficient Human Colon Cancer Cells.","authors":"Jingxue Shi, Qin He, Jie An, Hong Sun, Ying Huang, M Saeed Sheikh","doi":"10.4255/mcpharmacol.09.11","DOIUrl":"https://doi.org/10.4255/mcpharmacol.09.11","url":null,"abstract":"Sulindac, the non-steroidal anti-inflammatory drug has shown promise in the prevention of colon cancer but the molecular mechanisms by which it mediates such effects remain to be elucidated. Sulindac sulfide is the major active metabolite of sulindac and believed to be responsible for mediating the effects of sulindac. Previously, our group and others have shown that sulindac sulfide induces apoptosis by engaging death receptor and mitochondrial pathways and that a cross-talk exists between these two pathways during sulindac sulfide-induced apoptosis. Second mitochondrial-derived activator (Smac) is an important pro-apoptotic molecule that activates caspases by antagonizing the inhibitors of apoptosis (IAPs). In this study, we have utilized Smac-proficient and -deficient human colon cancer cells to investigate the role of Smac during sulindac sulfide-induced apoptosis and found that Smac deficiency affects sulindac sulfide-induced apoptosis in human colon cancer cells. Sulindac sulfide-induced apoptosis is coupled with upregulation of death receptor 5 (DR5), and activation of caspases 3, 9 and 8 in Smac-proficient cells. In Smac-deficient cells, although sulindac sulfide-induced DR5 upregulation is not altered, activation of caspases 3, 9 and 8 is affected. Smac deficiency also abrogates sulindac sulfide-induced cytochrome c release from mitochondria into cytosol. Our results, therefore, demonstrate that Smac is involved in sulindac sulfide-induced apoptotic signal transduction in human colon cancer cells and highlight the existence of a potential cross-talk between Smac and cytochrome c.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 2","pages":"92-97"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858416/pdf/nihms-139542.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28946918","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: 8

RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking. RanGTPase:核细胞质运输的关键调控因子。

Molecular and cellular pharmacology Pub Date : 2009-01-01 DOI: 10.4255/mcpharmacol.09.19

Ki Lui, Ying Huang

{"title":"RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking.","authors":"Ki Lui, Ying Huang","doi":"10.4255/mcpharmacol.09.19","DOIUrl":"https://doi.org/10.4255/mcpharmacol.09.19","url":null,"abstract":"RanGTPase belongs to the Ras superfamily of small GTPases. It possesses a distinctive acidic C-terminal DEDDDL motif and predominantly localizes to the nucleus. RanGTPase is known to regulate nucleocytoplasmic trafficking as well as mitotic spindle and nuclear envelope formation. Ran-directed nucleocytoplasmic trafficking is an energy-dependent directional process that also depends on nuclear import or export signals. Ran-directed nucleocytoplasmic trafficking is also facilitated by several cellular components, including RanGTPase, karyopherins, NTF2 and nucleoporins. GTP-bound Ran is asymmetrically distributed in the nucleus, while GDP-bound Ran is predominantly cytoplasmic. Controlled by RanGEF and RanGAP, RanGTPase cycles between the GDP- and GTP-bound states enabling it to shuttle cargoes in an accurate spatial and temporal manner. RanGTPase plays a role in the nuclear import in such a way that GTP-bound Ran dissociates importin:cargo complex in the nucleus and recycles importin back to cytoplasm. Likewise, RanGTPase plays a role in the nuclear export in such a way that nuclear GTP-bound Ran triggers the aggregation of Ran:exportin:cargo trimeric complex which is then transported to cytoplasm while hydrolysis of RanGTP to RanGDP releases the export cargoes in cytoplasm. RanGTPase has been reported to be essential for cell viability and its over-expression is linked to tumorigenesis. Thus, RanGTPase plays a crucial role in regulating key cellular events and alterations in its expression may lead to cancer development and/or progression.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 3","pages":"148-156"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839366/pdf/nihms137156.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28843241","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: 40

Nucleolin Binds to the Proliferating Cell Nuclear Antigen and Inhibits Nucleotide Excision Repair. 核蛋白与增殖细胞核抗原结合并抑制核苷酸切除修复。

Molecular and cellular pharmacology Pub Date : 2009-01-01 DOI: 10.4255/mcpharmacol.09.17

Chonglin Yang, Myoung Sook Kim, Devulapalli Chakravarty, Fred E Indig, France Carrier

{"title":"Nucleolin Binds to the Proliferating Cell Nuclear Antigen and Inhibits Nucleotide Excision Repair.","authors":"Chonglin Yang, Myoung Sook Kim, Devulapalli Chakravarty, Fred E Indig, France Carrier","doi":"10.4255/mcpharmacol.09.17","DOIUrl":"https://doi.org/10.4255/mcpharmacol.09.17","url":null,"abstract":"Nucleolin is over-expressed in malignant tumors and is used as a marker for cell proliferation and to reliably predict tumor growth rate. However, it is not known whether nucleolin expression is directly involved in or is a consequence of carcinogenesis. Using GST-pull down assays, we have determined that the recombinant nucleolin interacts with the Proliferating Cell Nuclear Antigen (PCNA). Co-immunoprecipitation assays indicate that the nucleolin-PCNA interaction also occurs in intact cells and this interaction increases after exposure of colon carcinoma RKO cells to UV radiation. Moreover, our data indicate that PCNA and nucleolin co-localize in some areas within the RKO cell nuclei. The functional significance of this interaction is evaluated on Nucleotide Excision Repair (NER) since PCNA is a primary mediator of this cellular function. Our data indicate that overexpression of nucleolin decreases the repair efficiency of UV damaged plasmid DNA in RKO cells. Co-transfection with PCNA can rescue this effect in vivo. Furthermore, reduction of nucleolin protein levels increases DNA repair efficiency in RKO and CHO cells and consequently increases cell survival. These data indicate that the direct interaction of nucleolin with PCNA inhibits NER efficiency of UV damaged DNA. This effect could contribute to carcinogenesis and aging in cells over-expressing nucleolin.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 3","pages":"130-137"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844761/pdf/nihms-183425.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28876009","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: 24

Developing Antiepileptogenic Drugs for Acquired Epilepsy: Targeting the Mammalian Target of Rapamycin (mTOR) Pathway. 开发抗癫痫药物治疗获得性癫痫:靶向雷帕霉素(mTOR)通路的哺乳动物靶点。

Molecular and cellular pharmacology Pub Date : 2009-01-01 DOI: 10.4255/mcpharmacol.09.16

Ling-Hui Zeng, Nicholas R Rensing, Michael Wong

{"title":"Developing Antiepileptogenic Drugs for Acquired Epilepsy: Targeting the Mammalian Target of Rapamycin (mTOR) Pathway.","authors":"Ling-Hui Zeng, Nicholas R Rensing, Michael Wong","doi":"10.4255/mcpharmacol.09.16","DOIUrl":"https://doi.org/10.4255/mcpharmacol.09.16","url":null,"abstract":"While current medications for epilepsy are primarily symptomatic treatments that suppress seizures, one of the main goals of future drug development in epilepsy is the identification of antiepileptogenic or disease-modifying therapies that can completely prevent epilepsy or slow its progression. A rational antiepileptogenic strategy is to target primary cell signaling pathways that initially trigger the downstream mechanisms causing epileptogenesis. Recent work implicates the mammalian target of rapamycin (mTOR) pathway as mediating epileptogenesis in a genetic epilepsy, Tuberous Sclerosis Complex (TSC), and suggests that mTOR inhibitors, such as rapamycin, may have antiepileptogenic properties for epilepsy in TSC. As mTOR regulates multiple cellular functions that may contribute to epileptogenesis in general, including ion channel expression, synaptic plasticity, and programmed cell death, mTOR inhibitors might also represent an effective antiepileptogenic therapy for other, more common types of epilepsy, such as acquired epilepsies due to brain injuries. Here, we describe evidence from a recently-published study that mTOR mediates epileptogenesis in a popular animal model of acquired limbic epilepsy due to brain injury following kainate-induced status epilepticus, and that rapamycin has antiepileptogenic effects in this model. Furthermore, putative pathways and mechanisms upstream and downstream from mTOR involved in epileptogenesis in the kainite model are considered, identifying possible additional therapeutic targets. Finally, the potential translational applications of this and other animal model data for developing antiepileptogenic therapies for people with acquired epilepsy due to brain injury are discussed.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 3","pages":"124-129"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858431/pdf/nihms183422.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28946924","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: 46

Extraction, Characterization, Stability and Biological Activity of Flavonoids Isolated from Chamomile Flowers. 洋甘菊黄酮类化合物的提取、表征、稳定性及生物活性研究。

Molecular and cellular pharmacology Pub Date : 2009-01-01 DOI: 10.4255/mcpharmacol.09.18

Janmejai K Srivastava, Sanjay Gupta

{"title":"Extraction, Characterization, Stability and Biological Activity of Flavonoids Isolated from Chamomile Flowers.","authors":"Janmejai K Srivastava, Sanjay Gupta","doi":"10.4255/mcpharmacol.09.18","DOIUrl":"https://doi.org/10.4255/mcpharmacol.09.18","url":null,"abstract":"Dried flowers of Chamomile (Matricaria chamomilla) are largely used for their medicinal properties. In the present study, we examined the pharmacological properties of aqueous and methanolic fraction isolated from two varieties of German chamomile. HPLC-MS analysis of chamomile extract confirmed apigenin-7-O-glucoside as the major constituent of chamomile; some minor glycoside components were observed along with essential oils. These glucosides are highly stable in solution at different temperature range and their degradation occurs after long-term storage and extraction conditions at different pH and solvent. Methanolic fraction isolated from chamomile flowers demonstrated higher biologic response in inhibiting cell growth and causing induction of apoptosis in various human cancer cell lines compared to aqueous chamomile fraction. Apigenin glucosides inhibited cancer cell growth through deconjugation of glycosides that occurs in the cellular compartment to produce aglycone, apigenin. Taken together, the pharmacological profile of chamomile extract was dependent upon extraction process, storage conditions which affected the biological activity.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 3","pages":"138"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809371/pdf/nihms136611.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28668268","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: 124

Abuse Potential of Soma: the GABA(A) Receptor as a Target. 索玛的滥用潜力：以 GABA（A）受体为目标。

Molecular and cellular pharmacology Pub Date : 2009-01-01

Lorie A Gonzalez, Michael B Gatch, Michael J Forster, Glenn H Dillon

{"title":"Abuse Potential of Soma: the GABA(A) Receptor as a Target.","authors":"Lorie A Gonzalez, Michael B Gatch, Michael J Forster, Glenn H Dillon","doi":"","DOIUrl":"","url":null,"abstract":"Soma(®) (carisoprodol) is an increasingly abused, centrally-acting muscle relaxant. Despite the prevalence of carisoprodol abuse, its mechanism of action remains unclear. Its sedative effects, which contribute to its therapeutic and recreational use, are generally attributed to the actions of its primary metabolite, meprobamate, at GABA(A) receptors (GABA(A)R). Meprobamate is a controlled substance at the federal level; ironically, carisoprodol is not currently classified as such. Using behavioral and molecular pharmacological approaches, we recently demonstrated carisoprodol, itself, is capable of modulating GABA(A)R function in a manner similar to central nervous system depressants. Its functional similarities with this highly addictive class of drugs may contribute to the abuse potential of carisoprodol. The site of action of carisoprodol has not been identified; based on our studies, interaction with benzodiazepine or barbiturate sites is unlikely. These recent findings, when coupled with numerous reports in the literature, support the contention that the non-controlled status of carisoprodol should be reevaluated.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 4","pages":"180-186"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858432/pdf/nihms183444.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28945829","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: 0

A Potential Preclinical Migraine Model: CGRP-Sensitized Mice. 一个潜在的临床前偏头痛模型:cgrp致敏小鼠。

Molecular and cellular pharmacology Pub Date : 2009-01-01

Andrew F Russo, Adisa Kuburas, Eric A Kaiser, Ann C Raddant, Ana Recober

{"title":"A Potential Preclinical Migraine Model: CGRP-Sensitized Mice.","authors":"Andrew F Russo, Adisa Kuburas, Eric A Kaiser, Ann C Raddant, Ana Recober","doi":"","DOIUrl":"","url":null,"abstract":"The neuropeptide calcitonin gene-related peptide (CGRP) plays a key role in migraine. However, a major challenge for studying CGRP actions is the lack of animal models for migraine. Clinical studies suggested that migraineurs are more sensitive to CGRP than people who do not suffer from migraine. We therefore generated a transgenic mouse that is sensitized to CGRP (nestin/hRAMP1 mice). The mice have elevated expression of a subunit of the CGRP receptor, human receptor activity-modifying protein 1 (hRAMP1). Nestin/hRAMP1 mice have two symptoms of migraine: photophobia and mechanical allodynia. The light aversion was greatly enhanced by intracerebroventricular administration of CGRP. CGRP had little effect on motility in the light zone, but once in the dark, the mice moved less than controls. The CGRP-induced light aversion was attenuated by co-administration of the CGRP receptor antagonist olcegepant. These findings suggest that CGRP acts as a neuromodulator to increase sensory responses and that regulation of a single gene, hRAMP1, could potentially contribute to migraine susceptibility.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 5","pages":"264-270"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844716/pdf/nihms183451.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28875504","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: 0