Will Quantitative Proteomics Redefine Some of the Key Concepts in Skeletal Muscle Physiology?

Abstract

Molecular and cellular biology methodology is traditionally based on the reasoning called “the mechanistic explanation”. In practice, this means identifying and selecting correlations between biological processes which result from our manipulation of a biological system. In theory, a successful application of this approach requires precise knowledge about all parameters of a studied system. However, in practice, due to the systems’ complexity, this requirement is rarely, if ever, accomplished. Typically, it is limited to a quantitative or semi-quantitative measurements of selected parameters (e.g., concentrations of some metabolites), and a qualitative or semi-quantitative description of expression/post-translational modifications changes within selected proteins. A quantitative proteomics approach gives a possibility of quantitative characterization of the entire proteome of a biological system, in the context of the titer of proteins as well as their post-translational modifications. This enables not only more accurate testing of novel hypotheses but also provides tools that can be used to verify some of the most fundamental dogmas of modern biology. In this short review, we discuss some of the consequences of using quantitative proteomics to verify several key concepts in skeletal muscle physiology.

Aging‐associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte‐to‐neuron lactate shuttle

“…Up to date, almost all studies on brain energy proteome were performed using mass spectrometry analysis of spots cut from 2D‐PAGE after their densitometric measurement (for review see VanGuilder & Freeman, ). This makes these analyses partial and not really quantitative in terms used by biology and chemistry (for review see Gizak & Rakus, ). The newest, gel‐free, studies of hippocampal proteome have been dedicated to investigate Alzheimer's disease‐related changes and do not provide information about energy metabolism changes during aging (e.g., Neuner, Wilmott, Hoffmann, Mozhui, and Kaczorowski, ).…”

Proteomics Unveils Fibroblast–Cardiomyocyte Lactate Shuttle and Hexokinase Paradox in Mouse Muscles

“…Quantitative proteomics approaches allow not only testing of novel hypotheses but also provide tools that can be used to verify some of the most fundamental dogmas of biology (for example, see ref ). Quantitative mapping of tissue-specific proteomes at molar concentrations is the precondition to successful determine targets for pharmacological treatment.…”

Comprehensive Analysis of the Proteome and PTMomes of C2C12 Myoblasts Reveals that Sialylation Plays a Role in the Differentiation of Skeletal Muscle Cells

“…The C2C12 myoblast, an immortalized mouse cell line, is commonly used as a model system to study the molecular and biochemical properties of skeletal muscle and the process of skeletal muscle cell differentiation in culture . Skeletal muscle cell differentiation is a complicated process coordinated by several transcription factors, including some muscle-specific regulatory factors (MRFs), such as myoblast determination protein 1 (MyoD), myogenin (Myog), myogenic factor 5 (Myf5), myogenic factor 6 (Myf6), and myocyte-specific enhancer factors (MEFs), such as Mef2A and Mef2D. − The expression of these transcription factors is positively controlled by the P38 mitogen-activated protein kinase (MAPK) signaling pathway .…”