Affiliations: Departments of Biochemistry and Molecular Biology,
University of Louisville, Louisville, KY, USA | Department of Cell and Developmental Biology,
University of Louisville, KY, USA | Institute of Gerontology, University of Michigan, Ann
Arbor, MI, USA
Note: [] Corresponding author: Dr. Bruce M. Carlson, Institute of
Gerontology, 300 North Ingalls Bldg., # 913, University of Michigan, Ann Arbor,
Michigan 48109, USA. Tel.: +1 734 764 3493; Fax: +1 734 936 2116; E-mail:
brcarl@umich.edu
Abstract: Purpose: This study was designed to determine whether the
quantitative relationship between the levels of the eEF1A-1(developmental) and
eEF1A-2/S1 (adult) isoforms of peptide elongation factor remains stable after
denervation of skeletal muscle or whether in response to denervation the
relative amount of the developmental form would increase. In normal postnatal
rat muscle, eEF1A-2/S1 is the dominant form represented, and levels of eEF1A-1
are extremely low. Methods: One hind limb in young adult rats was permanently
denervated. Denervated and corresponding contralateral control muscles were
removed for biochemical and morphological analysis from 2 days to 25 months
after denervation. Results: By one month after denervation, relative levels of eEF1A-1
rose dramatically in relation to those of eEF1A-2/S1, and they remained high
throughout the remainder of the 25-month denervation period. Ultrastructural
analysis showed a complex mix of muscle fiber atrophy, dying muscle nuclei and
muscle fibers, and newly forming muscle fibers in the same tissue. Conclusions: As during muscle regeneration, levels of the
developmental eEF1A-1 isoform of peptide elongation factor greatly increased
relative to those of the adult eEF1A-2/S1 adult isoform following denervation
in rat muscles. However, in contrast to regeneration, the elevated level of
eEF1A-1 did not return to the basal minimal level. Since switching from eEF1A-1
to eEF1A-2/S1 is an indicator that terminal differentiated is completed, the
failure of eEF1A-1 to return to basal level may be indicative of the
persistence of an unstable tissue environment that includes muscle fiber
atrophy, degeneration and neomyogenesis. The specific cellular basis for the
increase in eEF1A-1 could not be determined from this study.
Keywords: skeletal muscle, denervation, peptide elongation factors, ultrastructure, rat
