Proteomes, Their Compositions and Their Sources.

Biological samples of human and animal origin are utilized in research for many purposes and in a variety of scientific fields, including mass spectrometry-based proteomics. Various types of samples, including organs, tissues, cells, body fluids such as blood, plasma, cerebrospinal fluid, saliva and semen, can be collected from humans or animals and processed for proteomics analysis. Depending on the physiological state and sample origin, collected samples are used in research and diagnostics for different purposes. In mass spectrometry-based proteomics, body fluids and tissues are commonly used in discovery experiments to search for specific protein markers that can distinguish physiological from pathophysiological states, which in turn offer new diagnosis strategies and help developing new drugs to prevent disease more efficiently. Cell lines in combination with technologies such as Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) have broader application and are used frequently to investigate the mechanism of a disease or to investigate for the mechanism of a drug function. All of these are important components for defining the mechanisms of disease, discovering new pharmaceutical treatments and finally testing side effects of newly discovered drugs.

Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency.

Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. Mat1a -/- mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteome/phosphoproteome in pre-disease and NASH Mat1a -/- mice, effects of SAMe administration, and compared to human nonalcoholic fatty liver disease (NAFLD). Mitochondrial and peroxisomal lipid metabolism proteins were altered in pre-disease mice and persisted in NASH Mat1a -/- mice, which exhibited more progressive alterations in cytoplasmic ribosomes, ER, and nuclear proteins. A common mechanism found in both pre-disease and NASH livers was a hyperphosphorylation signature consistent with casein kinase 2α (CK2α) and AKT1 activation, which was normalized by SAMe administration. This was mimicked in human NAFLD with a metabolomic signature (M-subtype) resembling Mat1a -/- mice. In conclusion, we have identified a common proteome/phosphoproteome signature between Mat1a -/- mice and human NAFLD M-subtype that may have pathophysiological and therapeutic implications.