Impaired inhibition of eIF4E-BP1 in skeletal muscle impacts stretch-shortening contraction maladaptation with age

Details

• Personal Author:
  Baker BA ; Cutlip, Robert G. ; Hollander MS
• Description:
  Specific molecular signaling mechanisms governing protein synthesis/degradation in skeletal muscle, which results in known adaptation or maladaptation following mechanical loading with aging are largely unknown. Purpose: The purpose of this study was to determine the morphological localization, distribution, and quantity of eIF4E and its regulator eIF4E-BP1 (regulators of the initiation of protein translation and the inhibition of initiation of protein translation, respectively) and their collective influence/s on young and old skeletal muscle of rats following chronic high-intensity mechanical loading via stretch-shortening contractions (SSCs). Methods: Left dorsiflexor muscles of young (12 weeks, N=6) and old (30 months, N=6) Fischer Brown Norway Hybrid rats, were loaded 3 times/week for 4.5-weeks using a protocol of 80 maximal SSCs per exposure in vivo. Transverse sections of the tibialis anterior muscle midbelly were cut and prepared for eIF4E and eIF4E-BP1 immunofluorescence and quantified via microscopy/imaging using standard stereology and densitometry. RESULTS: The % volume density of fibers per muscle section and the % affected area of eIF4E-BP1 both decreased significantly (approximately 16% and approximately 83%; p < 0.05 and p < 0.01), respectively) in young rats following SSC loading. Interestingly, following SSC loading the % affected area of eIF4E labeling remained elevated by approximately 150% (p < 0.05) in old compared with young rats following SSC loading. Furthermore, the % affected area of eIF4E-BP1 remained elevated by approximately 400% (p < 0.01) following SSC loading in old compared with young rats following SSC loading, while the % volume density also remained elevated by approximately 32% (p < 0.01) in old versus young rats. CONCLUSIONS: Our data suggest that SSC loading adaptation/maladaptation is significantly impacted by the distribution and quantity of eIF4E-BP1 and its regulation on the initiation of protein translation via sequestration of eIF4E. Collectively, these findings indicate that eIF4EBP1 may exert a chronic inhibitory effect on the availability of eIF4E to contribute to protein translation/synthesis in skeletal muscle of aged populations following repetitive mechanical loading. [Description provided by NIOSH]
• Subjects:
  Age Factors Aging Animals Laboratories Musculoskeletal Diseases Musculoskeletal System Occupational Health Safety
• Keywords:
  Age-factors Animal-studies Author Keywords: EIF4E EIF4E-BP1 Laboratory-animals Muscle-function Muscle-physiology Musculoskeletal-system Musculoskeletal-system-disorders Protein Translation Stretch-Shortening Contractions

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• ISSN:
  0195-9131
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Colorado ; Indiana ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 8 ; South Carolina ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  52
• Volume:
  43
• Issue:
  5
• NIOSHTIC Number:
  nn:20040271
• Citation:
  Med Sci Sports Exerc 2011 May; 43(5)(Suppl 1):52
• Email:
  bwb3@cdc.gov
• Federal Fiscal Year:
  2011
• Peer Reviewed:
  False
• Source Full Name:
  Medicine and Science in Sports and Exercise
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e87e0f42b86a4f017ac13cea6d43769b872f00a5768db262154c3b341865141a77a56e439f941516d19dea043d345639859fa09e3d1b62c3f824b490b1569e9d
• Download URL:
  https://stacks.cdc.gov/view/cdc/193210/cdc_193210_DS1.pdf
• File Type:
  [PDF - 45.06 KB ]