Differential modulation of α, β and γ enolase isoforms in regenerating mouse skeletal muscle

Abstract

Nothing is known about the expression of the glycolytic enzyme enolase in skeletal muscle alterations such as myofiber degeneration and regeneration. Enolase is a dimeric enzyme which exhibits cell type specific isoforms. The embryonic form, aa, remains expressed in most adult tissues, whereas a transition towards specific isoforms occurs during ontogenesis in two cell types with high energy requirements: ag and gg in neurons, ab and bb in striated muscle cells. During murine myogenesis, b enolase transcripts are detected early in the forming muscles, and the b gene is further upregulated at specific stages of muscle development. The a and b subunits exhibit characteristic developmental microheterogeneity patterns. High levels of b enolase subunits characterize the glycolytic fast-twitch fibers of adult muscles. We have investigated the expression of enolase subunits in a mouse experimental model of muscle regeneration. Following a single intramuscular injection of the necrotic agent cardiotoxin, we observed a rapid decrease in the level of the major muscle enolase subunit b, accounting for the drop in total enolase activity that correlated with the degeneration of myofibers. Concomitant with the regeneration of new fibers, b subunit levels began to increase, reaching normal values by 30 days after injury. Changes in the embryonic and ubiquitous subunit, a, mimicked those occurring during development by two aspects: modifications in electrophoretic variants and redistribution between soluble and insoluble compartments of muscle extracts. Imunocytochemical analyses of a and b enolase subunits first revealed a homogeneous labeling within myofibers. Striations characteristic of normal adult muscle tissue were visible again by day 14 after injury. A perinuclear a and b immunoreactivity was often observed in regenerating myofibers but its functional significance remains to be elucidated. Double labeling experiments with anti-g enolase and FITC-a bungarotoxin allowed us to follow the neuromuscular junction remodeling that occurs during muscle regeneration despite the absence of nerve injury.

Distribution of beta-enolase in normal and tumor rat cells.

“…We observed that the perinuclear immunoreactivity of β-enolase in the rat sarcoma cells was more intensive than in normal rat cells. This corresponds to other reports on the localization of mouse muscle enolase in regenerating tissue [1]. However other authors report a nuclear location of enolase molecules in rat neurons [21] and HeLa cells [22].…”

“…The ubiquitous αα isoform remains widely distributed in embryonic most adult cell types. In adult muscle tissues, the β-enolase subunit accumulates preferentially in fast-twitch fibres, where the ββ homodimer accounts for more than 90% of the total enolase activity [1].…”

Proteomic Analysis of Eggs from Mytilus edulis Females Differing in Mitochondrial DNA Transmission Mode

“…This is consistent with them being products of different genes or for example alternative splice variants, or post translational modifications of the same proteins. Evidence for independently regulated different genes is that multiple genetic isoforms have been reported for arginine kinase (65,66), enolase (67), and ferritin (68,69). For proteasome there are three different subunits in Table III.…”

Transgenic Mice Overexpressing BMP4 Develop a Fibrodysplasia Ossificans Progressiva (FOP)-Like Phenotype

“…Neuron-specific enolase (gamma enolase, NSE) is predominantly expressed by neurons and neuroendocrine cells, but much lower levels are also expressed by developing or injured striatal muscle cells, 17 by activated T cells, and by activated macrophages. 18 We initially constructed transgenic animals that overexpress either BMP4 (NSE-BMP4) or the BMP inhibitor noggin (NSEnoggin) under control of the NSE promoter to examine the role of BMP signaling in development of the brain.…”