TY - JOUR
T1 - Systems-Scale Analysis Reveals Pathways Involved in Cellular Response
A1 - Sun, Lijie
A1 - Li, Hong-Mei
A1 - Seufferheld, Manfredo J.
A1 - Walters, Kent R., Jr.
A1 - Margam, Venu M.
A1 - Jannasch, Amber
A1 - Diaz, Naomi
A1 - Riley, Catherine P.
A1 - Sun, Weilin
A1 - Li, Yueh-Feng
A1 - Muir, William M.
A1 - Xie, Jun
A1 - Wu, Jing
A1 - Zhang, Fan
A1 - Chen, Jake Y.
A1 - Barker, Eric L.
A1 - Adamec, Jiri
A1 - Pittendrigh, Barry R.
Y1 - 2011/04/20
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
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.
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.
JF - PLoS ONE
JA - PLoS ONE
VL - 6
IS - 4
UR - http://dx.doi.org/10.1371%2Fjournal.pone.0018215
SP - e18215
PB - Public Library of Science
M3 - doi:10.1371/journal.pone.0018215