title: Toxin injury-dependent switched expression between EF-1 alpha and its sister, S1, in rat skeletal muscle.
abstract: Elongation factor-1 alpha, (EF-1 alpha), a translation factor involved in peptide chain elongation, is found ubiquitously in all cells. Previously, we identified a highly homologous EF-1 alpha sister gene, S1, whose transcript is found in only three tissues: brain, heart, and muscle, where the tissue-specific expression of S1 is caused by its exclusive presence in cells such as neurons and myocytes. Using sequence-specific synthetic peptides, we have recently produced polyclonal antibodies that can distinguish the protein product of EF-1 alpha from that of its sister, S1. Results of Western blotting show that these two proteins appear in S1-positive muscle tissue in inverse relationship, i.e., when S1 protein is in abundance, EF-1 alpha protein is in contrast in low quantity, and vice versa. During early embryonic stages, EF-1 alpha is the predominant protein species, whereas S1 is hardly detectable. This high EF-1 alpha versus low S1 protein presence undergoes a switch in that by postnatal day 14, EF-1 alpha is scarce whereas S1 is abundant; thus, there is a development-dependent shift of EF-1 alpha/S1 ratio from high to low, and the low EF-1 alpha/S1 ratio is maintained in adulthood. In this report, we describe the reversal of the EF-1 alpha/S1 ratio from low to high during muscle injury (experimentally induced by Marcaine injection), and a return to the original low ratio once the injury is repaired by regeneration. In this injury condition, EF-1 alpha is rapidly upregulated immediately after the Marcaine treatment, possibly reflecting an injury-dependent response of regeneration. The increase of EF-1 alpha corresponds with a decrease of S1 protein presence, thus resulting in a change of EF-1 alpha/S1 ratio from low to high. However, the high EF-1 alpha/S1 ratio eventually reverts to low, when regeneration-associated proliferation ceases, and fully differentiated myotubes are reestablished in the injured cells. This result shows that: (1) a high EF-1 alpha/S1 ratio is an early molecular diagnostic marker for injury-elicited regeneration; and (2) when injury repair is accomplished, there is a reversion to the low EF-1 alpha/S1 ratio, reflecting the restoration of the muscle fiber to the preinjury functional status. Results presented here not only show that a high EF-1 alpha/S1 ratio is a molecular marker for injured muscle, but also reveal the underpinning translational regulation in muscle during injury.
authors.affiliation: Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Quebéc, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Khalyfa
authors.forename: B M
authors.initials: BM
authors.lastname: Carlson
authors.forename: J A
authors.initials: JA
authors.lastname: Carlson
authors.forename: E
authors.initials: E
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000779:Anesthetics, Local; D000818:Animals; D015153:Blotting, Western; D002045:Bupivacaine; D007511:Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D020648:Peptide Elongation Factor 1 / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*
chemical_list: D000199:Actins; D000779:Anesthetics, Local; D020648:Peptide Elongation Factor 1; D010446:Peptide Fragments; C033025:actin subfragments; D002045:Bupivacaine