Generally detected proteins in comparative proteomics – A matter of cellular stress response?

Abstract

The specificity of proteins identified by proteomics as biomarkers for defined conditions or as components of biological processes and pathways is crucial. We critically reviewed differentially expressed proteins from comparative proteomic studies identified by 2-DE followed by MS, especially with MALDI technique. Based on 66 of those studies, a list of 44 proteins is presented as generally detected proteins regardless of species, in vivo or in vitro conditions, tissues and organs, and experimental objective. Similarly, a list of 28 generally detected protein families is presented. The enriched functions linked to these generally detected proteins reveal that there are some common biological features beyond the technical limitations. Cellular stress response can be the universal reason as to why these proteins are generally expressed differentially. Using those proteins as biomarkers for cellular processes other than stress response should be done with caution. In future proteomic studies more profound approaches should be applied to look beyond these proteins to find specific biomarkers. Our results are discussed in relation to a recent viewpoint publication by Petrak et al. [Proteomics 2008, 8, 1744-1749].

Considerations for the use of transcriptomics in identifying the ‘genes that matter’ for environmental adaptation

“…Gene ontology classification and tests for functional enrichment of the 44 most frequently detected proteins yield striking similarity to ontologies comprising the cellular stress response ( Fig. 4; Wang et al, 2009b). While similar meta-analyses are not available for transcriptomic datasets, biases in the proteomic literature are the result of the same data-filtering practices frequently implemented in transcriptomics that emphasize highly expressed and easily annotated genes.…”

“…Similar analytical approaches have biased proteomic datasets toward the repeated identification of cellular stress response proteins. Meta-analyses of the comparative proteomics literature have generated a list of repeatedly detected proteins that are consistently differentially expressed independent of target species, in vivo or in vitro conditions, tissue or organ assayed, or experimental objective (Petrak et al, 2008;Mariman, 2009;Wang et al, 2009b). These proteins account for 23.2% of those considered differentially expressed, but represent only 4.9% of unique proteins across the species assayed.…”

“…Comparative approaches that relate transcriptional responses to the environment between one or more taxons offer considerable improvement over single-species analyses (Whitehead, 2012). Comparative experiments allow conserved responses to environmental change to be separated from responses that are exclusive to particular species or populations (Stillman and Tagmount, 2009 Wang et al (2009b). Stars indicate that this functional category is also part of the minimal stress proteome defined by Kültz (2005).…”

Proteomic responses to environmentally induced oxidative stress

“…As protein maturation in the ER generates H 2 O 2 , a decrease in protein synthesis could lower the rate of ROS production. The importance of this link is further supported by the inclusion of the ER chaperones Grp78, PDIs and PPIases and the antioxidant protein Prx, together with SOD and ALDH, in the proposed minimal stress proteome of organisms (Kültz, 2005;Petrak et al, 2008;Wang et al, 2009). …”

In Vitro, In Vivo Comparison of Cyclosporin A Induced Hepatic Protein Expression Profiles

“…The differential expressions of proteins from energy metabolism are probably a first indication of a toxicological response. However, several proteins from energy metabolism are often detected in comparative proteomics and considered as proteins from a general stress response [39]. Therefore using those proteins as specific markers for cholestasis should be done with caution.…”