Dataset Information

Systems-scale analysis reveals pathways involved in cellular response to methamphetamine.

ABSTRACT:

Background

Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced.

Methodology/results

We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis/contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level.

Conclusion

Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions.

SUBMITTER: Sun L

PROVIDER: S-EPMC3080363 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Publications

Systems-scale analysis reveals pathways involved in cellular response to methamphetamine.

Sun Lijie L Li Hong-Mei HM Seufferheld Manfredo J MJ Walters Kent R KR Margam Venu M VM Jannasch Amber A Diaz Naomi N Riley Catherine P CP Sun Weilin W Li Yueh-Feng YF Muir William M WM Xie Jun J Wu Jing J Zhang Fan F Chen Jake Y JY Barker Eric L EL Adamec Jiri J Pittendrigh Barry R BR

PloS one 20110420 4

<h4>Background</h4>Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerou ...[more]

PMID: 21533132

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Dataset Information

Systems-scale analysis reveals pathways involved in cellular response to methamphetamine.

Background

Methodology/results

Conclusion

Publications

Systems-scale analysis reveals pathways involved in cellular response to methamphetamine.

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