Mitochondria are key organelles in mammary cells in responsible for a number of cellular functions including cell survival and energy metabolism. Moreover, mitochondria are one of the major targets under doxorubicin treatment. In this study, low-abundant mitochondrial proteins were enriched for proteomic analysis with the state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assistant laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the mitochondrial protein profiling changes in response to the development of doxorubicin resistance in human uterine cancer cells. The mitochondrial proteomic results demonstrate more than fifteen hundred protein features were resolved from the equal amount pooled of three purified mitochondrial proteins and 101 differentially expressed spots were identified. In which, 39 out of these 101 identified proteins belong to mitochondrial proteins. Mitochondrial proteins such as acetyl-CoA acetyltransferase (ACAT1) and malate dehydrogenase (MDH2) have not been reported with the roles on the formation of doxorubicin resistance in our knowledge. Further studies have used RNA interference and cell viability analysis to evidence the essential roles of ACAT1 and MDH2 on their potency in the formation of doxorubicin resistance through increased cell viability and decreased cell apoptosis during doxorubicin treatment. To sum up, our current mitochondrial proteomic approaches allowed us to identify numerous proteins, including ACAT1 and MDH2, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for the treatment of doxorubicin-resistant uterine cancer.

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Down syndrome is one of the most frequent chromosomal disorders, with a prevalence of approximately 1/500 to 1/800, depending on the maternal age distribution of the pregnant population. However, few reliable protein biomarkers have been used in the diagnosis of this disease. Recent progress in quantitative proteomics has offered opportunities to discover biomarkers for tracking the progression and for understanding the molecular mechanisms of Down syndrome. In the present study, placental samples were analyzed by fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) and differentially expressed proteins were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In total, 101 proteins have been firmly identified representing 80 unique gene products. These proteins mainly function in cytoskeleton structure and regulation (such as vimentin and Profilin-1). Additionally, our quantitative proteomics approach has identified numerous previously reported Down syndrome markers, such as myelin protein. Here we present several Down syndrome biomarkers including galectin-1, ataxin-3 and sprouty-related EVH1 domain-containing protein 2 (SPRED2), which have not been reported elsewhere and may be associated with the progression and development of the disease. In summary, we report a comprehensive placenta-based proteomics approach for the identification of potential biomarkers for Down syndrome, in which serum amyloid P-component (APCS) and ataxin-3 have been shown to be up-regulated in the maternal peripheral plasma of Down syndrome cases. The potential of utilizing these markers for the prognosis and screening of Down syndrome warrants further investigation.

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