Pub Date : 2007-11-07DOI: 10.2174/1874143600701010019
S. Lecht, H. Arien-Zakay, R. Tabakman, Hao Jiang, D. Fink, P. Lazarovici
PC12 clones are established neuronal models to investigate mechanisms involved in the cross-talk between the neurotrophins and drugs. Chronic treatment of PC12 cells with the glucocorticoid agonist drug, dexamethasone (Dex), elicited a 50% decrease in the selective binding of 125 I-NGF along with a reduction in the NGF receptor p75 NTR mRNA and protein levels, suggesting a transcriptional mechanism. This down regulation of p75 NTR was antagonized by the glu- cocorticoid type II receptor (GR-2), RU-38486 but not by the minerallocorticoid receptor, RU-28318, antagonists. This process was associated with increased autophosphorylation of the NGF receptor, TrkA. Chronic treatment of PC12 with Dex abolished the NGF-induced proliferation of the cells after 20 hours and inhibited by 45% the neurite elongation after 96 hours. RU-38486 blocked Dex-induced shift of PC12 cells from dopaminergic to noradrenergic phenotype. Dex- induced down regulation of p75 NTR receptor is mediated by GR-2 and is correlated with disruption of NGF induced prolif-
{"title":"Dexamethasone-Induced Down-Regulation of Nerve Growth Factor Receptor p75NTR is Mediated by Glucocorticoid Type II Receptor in PC12 Cell Model","authors":"S. Lecht, H. Arien-Zakay, R. Tabakman, Hao Jiang, D. Fink, P. Lazarovici","doi":"10.2174/1874143600701010019","DOIUrl":"https://doi.org/10.2174/1874143600701010019","url":null,"abstract":"PC12 clones are established neuronal models to investigate mechanisms involved in the cross-talk between the neurotrophins and drugs. Chronic treatment of PC12 cells with the glucocorticoid agonist drug, dexamethasone (Dex), elicited a 50% decrease in the selective binding of 125 I-NGF along with a reduction in the NGF receptor p75 NTR mRNA and protein levels, suggesting a transcriptional mechanism. This down regulation of p75 NTR was antagonized by the glu- cocorticoid type II receptor (GR-2), RU-38486 but not by the minerallocorticoid receptor, RU-28318, antagonists. This process was associated with increased autophosphorylation of the NGF receptor, TrkA. Chronic treatment of PC12 with Dex abolished the NGF-induced proliferation of the cells after 20 hours and inhibited by 45% the neurite elongation after 96 hours. RU-38486 blocked Dex-induced shift of PC12 cells from dopaminergic to noradrenergic phenotype. Dex- induced down regulation of p75 NTR receptor is mediated by GR-2 and is correlated with disruption of NGF induced prolif-","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"26 1","pages":"19-26"},"PeriodicalIF":0.0,"publicationDate":"2007-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88475795","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}
Pub Date : 2007-10-26DOI: 10.2174/1874143600701010013
Sanneke A. M. van Vliet, R. Vanwersch, M. Jongsma, J. Gugten, B. Olivier, I. Philippens
The present medication in Parkinson's disease (PD) is unable to stop or slow down the progression of the dis- ease. Therefore pharmacological intervention at crucial steps in the neuronal cell death processes would be a better stra- tegy. Cannabinoids are potent neuroprotective compounds in models of oxidative stress and excitotoxicity and offer po- tential protection in models of PD. Therefore the present study determines the neuroprotective effects of � 9 - tetrahydrocannabinol (� 9 -THC) in the marmoset 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model on beha- vior and pathology. Twelve marmoset monkeys were treated with a total cumulative dose of 6 mg/kg MPTP in 9 days. Seven of these animals received simultaneously a daily oral dose of � 9 -THC (4 mg/kg) and five animals received simulta- neously vehicle for 27 days. The parkinsonian symptoms were observed daily and locomotor activity and hand-eye coor- dination were tested once a week during the experimental period. Postmortem, dopamine levels in the striatum were ana- lyzed and tyrosine hydroxylase immunohistochemistry was applied to determine viable dopaminergic neurons in the sub- stantia nigra. � 9 -THC has no protective effects on any parameter. These negative results might be related to the severity of the cell death induction by MPTP in relation to the low dose of � 9 -THC used in this Parkinson model.
{"title":"Neuroprotective Effects of Delta-9-Tetrahydrocannabinol in a Marmoset Parkinson Model","authors":"Sanneke A. M. van Vliet, R. Vanwersch, M. Jongsma, J. Gugten, B. Olivier, I. Philippens","doi":"10.2174/1874143600701010013","DOIUrl":"https://doi.org/10.2174/1874143600701010013","url":null,"abstract":"The present medication in Parkinson's disease (PD) is unable to stop or slow down the progression of the dis- ease. Therefore pharmacological intervention at crucial steps in the neuronal cell death processes would be a better stra- tegy. Cannabinoids are potent neuroprotective compounds in models of oxidative stress and excitotoxicity and offer po- tential protection in models of PD. Therefore the present study determines the neuroprotective effects of � 9 - tetrahydrocannabinol (� 9 -THC) in the marmoset 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model on beha- vior and pathology. Twelve marmoset monkeys were treated with a total cumulative dose of 6 mg/kg MPTP in 9 days. Seven of these animals received simultaneously a daily oral dose of � 9 -THC (4 mg/kg) and five animals received simulta- neously vehicle for 27 days. The parkinsonian symptoms were observed daily and locomotor activity and hand-eye coor- dination were tested once a week during the experimental period. Postmortem, dopamine levels in the striatum were ana- lyzed and tyrosine hydroxylase immunohistochemistry was applied to determine viable dopaminergic neurons in the sub- stantia nigra. � 9 -THC has no protective effects on any parameter. These negative results might be related to the severity of the cell death induction by MPTP in relation to the low dose of � 9 -THC used in this Parkinson model.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"79 1","pages":"13-18"},"PeriodicalIF":0.0,"publicationDate":"2007-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83908957","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}
Pub Date : 2007-09-27DOI: 10.2174/1874143600701010001
Zihua Wang, S. Chong, Caroline G. L. Lee
To evaluate the usefulness of the two public databases, HapMap and Perlegen, in facilitating studies associating polymorphisms in these genes with drug response, we examined 111 single-nucleotide-polymorphisms from 13 ABC- transporter genes in Singaporean-Chinese, European-Americans and African-Americans. We found that genotype data from the HapMap/Perlegen databases are generally transferable to different sampling of the same population and to simi- lar populations residing elsewhere. However, not all ABC-transporter family genes are amenable to SNP-tagging due to the low tagging-efficiency of low-LD genes resulting in negligible cost-savings. Hence, alternative approaches may have to be explored for low-LD ABC genes.
{"title":"Characterization of Single Nucleotide Polymorphisms in 13 Members of the ABC Drug Transporter Genes in Three Different Populations","authors":"Zihua Wang, S. Chong, Caroline G. L. Lee","doi":"10.2174/1874143600701010001","DOIUrl":"https://doi.org/10.2174/1874143600701010001","url":null,"abstract":"To evaluate the usefulness of the two public databases, HapMap and Perlegen, in facilitating studies associating polymorphisms in these genes with drug response, we examined 111 single-nucleotide-polymorphisms from 13 ABC- transporter genes in Singaporean-Chinese, European-Americans and African-Americans. We found that genotype data from the HapMap/Perlegen databases are generally transferable to different sampling of the same population and to simi- lar populations residing elsewhere. However, not all ABC-transporter family genes are amenable to SNP-tagging due to the low tagging-efficiency of low-LD genes resulting in negligible cost-savings. Hence, alternative approaches may have to be explored for low-LD ABC genes.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"30 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2007-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89410366","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：