less likely to be false positives and may reflect biologically relevant links, thus presenting a reliable interactome for further experimental validation. For example, in a recent meta analysis of 300 tis sue samples of gastric cancer, this hypothesis www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html helped to identify a functional link between prognostic marker PLA2G2A and the EphB2 receptor. Second, network intersections account for putative platform or experi ment dependent variability between multiple microarray datasets. Third, due to the heterogeneous nature of physiological LVH models, conserved co expressions provide an overview of common regulatory mechanisms. These assumptions were confirmed using automated PubMed queries, whereby each gene in the Conserved network was searched in the context of hypertrophy, heart, or heart failure.

Indeed, 933 out of 2128 genes in the Conserved network had at least one abstract per search term while 50 of those have at least one hundred abstracts for all terms, suggesting that the Conserved network provides an acceptable coverage of current molecular knowledge of cardiac biology. The Conserved network may be used to describe the regulatory mechanisms underpinning the cardiac remodel ing response to physiological stress. Oxidative phosphory lation was noted as one of the most abundant KEGG pathways. The most over represented members of this pathway were genes encoding subunits of mitochondrial cytochrome c oxidase. COX is localized to the inner membrane of mitochondria and is the last component of respiratory chain.

To sustain respiration, this enzyme catalyzes the transfer of electrons from cytochrome c to molecular oxygen and facilitates the aerobic production of ATP by ATPsynthase. To maintain efficient cardiac contractility under Brefeldin_A increased energetic demand, the regulation of COX function must be preserved. In post myocardial infarction this mechanism is disrupted by the generation of reactive oxygen species such as superoxide, leading to a marked loss of COX activity. These results are consistent with the well established con cept that suppression of mitochondrial energy metabolism can lead to depression of cardiac contractile function. The Conserved network was useful in the delineation of the cardiac response to increased protein synthesis and energy deprivation through activation of autophagy.

This is a highly conserved cellular pro survival www.selleckchem.com/products/Bicalutamide(Casodex).html mechanism for bulk lysosomal degradation of cytoplasmic components that mobilizes energy resources in response to starvation or hypoxia. Autophagy also has a protein quality con trol housekeeping function. The Conserved network identified two key genes related to autophagic processes, Atg5 and Becn1. Both of these genes were topologically central to the Con served network, implicating them in critical media tion of network information flow. Recent studies in mice with temporally controlled cardiac specific deficiency of Atg5 demonstrated that Atg5 was essential for normal physiological growth and function of