Dataset Information

C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.

ABSTRACT: Recently, association of an interleukin-1A promoter polymorphism (-889, thymine/thymine (T/T)) with Alzheimer's disease was reported, suggesting that this cytokine may play an important role in disease development. To understand the mechanism underlying the interleukin-1A promoter's role in Alzheimer's disease, a study comparing promoter function of an interleukin-1A polymorphism was performed in the SVG astroglia cell line. The effects of thymine and cytosine on transcriptional activity of the interleukin-1A promoter were analyzed by testing luciferase-reporter activity in transfected SVG cells. Our results demonstrate that cytosine/thymine conversion increases activity of the interleukin-1A promoter in SVG cells. Both sodium salicylate and lovastatin are able to block induced promoter activities in astroglial cells. Induced promoter activity by the polymorphism (T/T) may result in the upregulation of interleukin-1alpha protein and "cytokine cycle" amplification, which may promote disease development.

SUBMITTER: Wei X

PROVIDER: S-EPMC1850933 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.

Wei Xing X Chen Xianming X Fontanilla Christine C Zhao Liming L Liang Zhong Z Dodel Richard R Hampel Hampel H Farlow Martin M Du Yansheng Y

Life sciences 20061223 12

Recently, association of an interleukin-1A promoter polymorphism (-889, thymine/thymine (T/T)) with Alzheimer's disease was reported, suggesting that this cytokine may play an important role in disease development. To understand the mechanism underlying the interleukin-1A promoter's role in Alzheimer's disease, a study comparing promoter function of an interleukin-1A polymorphism was performed in the SVG astroglia cell line. The effects of thymine and cytosine on transcriptional activity of the ...[more]

PMID: 17257626

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Project description:Human cytomegalovirus (HCMV) is a large DNA herpesvirus that is highly prevalent in the human population. HCMV can result in severe direct and indirect pathologies under immunosuppressed conditions and is the leading cause of birth defects related to infectious disease. Currently, the effect of HCMV infection on host cell metabolism as an increase in glycolysis during infection has been defined. We have observed that oxidative phosphorylation is also increased. We have identified morphological and functional changes to host mitochondria during HCMV infection. The mitochondrial network undergoes fission events after HCMV infection. Interestingly, the network does not undergo fusion. At the same time, mitochondrial mass and membrane potential increase. The electron transport chain (ETC) functions at an elevated rate, resulting in the release of increased reactive oxygen species. Surprisingly, despite the stress applied to the host mitochondria, the network is capable of responding to and meeting the increased bioenergetic and biosynthetic demands placed on it. When mitochondrial DNA is depleted from the cells, we observed severe impairment of viral replication. Mitochondrial DNA encodes many of the ETC components. These findings suggest that the host cell ETC is essential to HCMV replication. Our studies suggest the host cell mitochondria may be a therapeutic target.IMPORTANCE Human cytomegalovirus (HCMV) is a herpesvirus present in up to 85% of some populations. Like all herpesviruses, HCMV infection is for life. No vaccine is currently available, neutralizing antibody therapies are ineffective, and current antivirals have limited long-term efficacy due to side effects and potential for viral mutation and resistance. The significance of this research is in understanding how HCMV manipulates the host mitochondria to support bioenergetic and biosynthetic requirements for replication. Despite a large genome, HCMV relies exclusively on host cells for metabolic functions. By understanding the dependency of HCMV on the mitochondria, we could exploit these requirements and develop novel antivirals.

Dataset Information

C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.

Publications

C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.

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