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音量 10, 問題 3 (2016)

ミニレビュー

Mini Review: Potential Role of Hormones in the Tumors of Neurofibromatosis Type-1

Mauro Geller, Lisa Oliveira, Karin Soares Cunha, Spyros Mezitis GE and Marcia Gonçalves Ribeiro

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder caused by mutations in the NF1 gene, and presents a very broad spectrum of clinical manifestations and severity, including dermal and plexiform neurofibromas. In this mini review we briefly address the findings present in the literature related to hormone receptors within these tumor types.

短いコミュニケーション

Frequency of ABCG2 421C>A Genetic Variant and The Efficiency of Treatment with Rosuvastatin in Kazakh Male Patients

Kozhakhmetov SS, Kushugulova AR, Kakimova AB, Saduakhassova SA, Urazova ?S, Khassenbekova ZHR, Kozhakhmetova SS, Beysembayeva SCH, Sibagatova AS, Tuleutayeva GK, Urazbayeva GS, Ongarbayeva AE, Yakovenko GI, Kissikova SL and Nurgozhin ?S

Rosuvastatin is one of the most effective lipid-lowering drugs. Nevertheless its activity varies in different populations. Important role in this belongs to ABCG2. The objective of this study was to determine the impact of ABCG2 genotype on therapeutic effect of rosuvastatin in Kazakh population. This study included 82 Kazakh patients with metabolic disorder undergoing 10 -20 mg/day of rosuvastatin therapy for 12 weeks. Our findings indicated that people with 421AA genotype had higher response to the drug. The frequency of minor alleles in the studied group was 29.5%.

研究論文

DNA Binding and its Degradation by the Neurotransmitter Serotonin and its Structural Analogues Melatonin and Tryptophan: Putative Neurotoxic Mechanism

Nida Rehmani, Mohd Farhan and Sheikh Mumtaz Hadi

Over the years, DNA damage has been suggested to be directly linked to mutagenesis, carcinogenesis and ageing. There is ample evidence suggesting that considerable DNA damage may be induced by metabolites produced during normal or aberrant metabolic processes. Herein, we examine the chemical basis of cytotoxicity of some endogenous metabolites. Towards this goal, we study the DNA reactive activities of the neurotransmitter serotonin and its structural analogues tryptophan and melatonin in the presence of copper. Fluorescence spectroscopy reveals a simple mode of interaction of these metabolites with calf thymus DNA and copper ions. The results of agarose gel electrophoresis demonstrate copper mediated strand scission in plasmid pBR322 DNA by these metabolites. Further, the relative DNA binding affinity order was affirmed using molecular docking studies involving the interaction of these metabolites with calf thymus DNA. We employ single cell alkaline gel electrophoresis and determine the relative efficiency of cellular DNA breakage as Serotonin>Melatonin>Tryptophan. We hypothesize that such cellular DNA breakage is mediated by mobilization of copper ions bound to chromatin. Consistent with previous observations that many known antioxidants of plant and animal origin also exhibit prooxidant properties, these metabolites might contribute to oxidative DNA breakage in the presence of redox active metals such as copper. Our findings reveal a putative mechanism by which some endogenous metabolites may cause DNA damage leading to mutations and genetic diseases.

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