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 inDrosophila 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.
Date of this Version
4-20-2011
DOI
10.1371/journal.pone.0018215
Recommended Citation
Sun, Lijie; Li, Hong-Mei; Seufferheld, Manfredo J.; Walters, Kent R. Jr; Margam, Venu M.; Jannasch, Amber; Diaz, Naomi; Riley, Catherine P.; Sun, Weilin; Li, Yueh-Feng; Muir, William M.; Xie, Jun; Wu, Jing; Zhang, Fan; Chen, Jake Y.; Barker, Eric L.; Adamec, Jiri; and Pittendrigh, Barry R., "Systems-Scale Analysis Reveals Pathways Involved in Cellular Response to Methamphetamine." (2011). Department of Animal Sciences Faculty Publications. Paper 9.
http://dx.doi.org/10.1371/journal.pone.0018215
Comments
This is the publisher pdf of Sun L, Li H-M, Seufferheld MJ, Walters KR Jr, Margam VM, et al. (2011) Systems-Scale Analysis Reveals Pathways Involved in Cellular Response to Methamphetamine. PLoS ONE 6(4): e18215 and is available at: 10.1371/journal.pone.0018215.