globalchange  > 气候变化事实与影响
DOI: 10.1289/ehp.1510308
论文题名:
A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases
作者: Patricia Ruiz; 1* Ally Perlina; 2* Moiz Mumtaz; 1; Bruce A. Fowler3
刊名: Environmental Health Perspectives
ISSN: 0091-7001
出版年: 2016
卷: Volume 124, 期:Issue 7
起始页码: 1034
语种: 英语
英文摘要: Background: A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published.

Objectives: We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases.

Methods: For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes.

Conclusions: Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies.
URL: http://dx.doi.org/10.1289/ehp.1510308
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/12332
Appears in Collections:气候变化事实与影响
气候变化与战略

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作者单位: 1Computational Toxicology and Methods Development Laboratory, Division of Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease Registry, Atlanta, Georgia, USA; 2Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA; 3Emory University Rollins School of Public Health, Atlanta, Georgia, USA

Recommended Citation:
Patricia Ruiz,1* Ally Perlina,2* Moiz Mumtaz,et al. A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases[J]. Environmental Health Perspectives,2016-01-01,Volume 124(Issue 7):1034
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