Publication Date

2014

Document Type

Honors Thesis

Department

Biochemistry

Keywords

Mitogen-activated protein kinases, Myogenesis, Myoblasts, Mice-Muscles, Mice-Genetics, Gene expression, Expression level, MAP kinases, Early myotube, Myotube, C2C12

Abstract

The mitogen-activated protein kinases (MAPKs) are a system of enzymes that form distinct signaling cascades within mammalian cells (Kyriakis and Avruch, 2012). MAPKs regulate diverse cellular programs including embryomyogenesis, proliferation, differentiation, and apoptosis, depending on the stimuli derived from the cell surface as well as the metabolic state and environment of the cell (Raman et al., 2007). The three major MAPK families include extracellular signal-regulated kinase (ERK) 1/2/5, p38 kinase (p38) α/β/γ/δ, and c-Jun N-terminal kinase (JNK) 1/2/3. Myogenesis is a complex and tightly regulated process, which begins with the commitment of an embryonic precursor cell to the myogenic lineage, followed by the proliferation and differentiation of committed myoblast into multinucleated myotubes and eventually, the development of muscle fibers (Knight and Kothary, 2011). The process of the early stage of myogenesis is modeled in vitro with the C2C12 skeletal muscle cell line, which is a subclone of C2 myoblasts derived from the thigh of an adult mouse (Yaffe and Saxel, 1977). C2C12 differentiates rapidly and recapitulates myogenesis that clearly demonstrates three distinct cell stages. In differentiation medium, proliferating embryonic myoblasts begin to fuse and differentiate into multinucleated early myotubes; then as late myotubes, they become highly branched and initiate myofibrillogenesis (Yoshida et al., 1998). The process of cell fusion during myogenesis is a cellular stressor and the cells may adapt to the mechanical stress by regulating the activities of the MAPKs. This study investigated whether the expression, phosphorylation, and activation of ERK1/2, ERK5, p38, and JNK1/2 would vary significantly during murine C2C12 myogenesis. C2C12 myoblasts were grown in 10%

Language

English

Comments

viii, 90 pages : illustrations (some color). Honors Project-Smith College, 2014. Includes bibliographical references (pages 82-90)

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