Excessive training is associated with endoplasmic reticulum stress but not apoptosis in the hypothalamus of mice

Appl Physiol Nutr Metab. 2017 Apr;42(4):354-360. doi: 10.1139/apnm-2016-0542. Epub 2016 Dec 5.

Abstract

Downhill running-based overtraining model increases the hypothalamic levels of IL-1β, TNF-α, SOCS3, and pSAPK-JNK. The aim of the present study was to verify the effects of 3 overtraining protocols on the levels of BiP, pIRE-1 (Ser724), pPERK (Thr981), pelF2α (Ser52), ATF-6, GRP-94, caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) proteins in the mouse hypothalamus. The mice were randomized into the control, overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. After the overtraining protocols (i.e., at the end of week 8), hypothalamus was removed and used for immunoblotting. The OTR/down group exhibited increased levels of all of the analyzed endoplasmic reticulum stress markers in the hypothalamus at the end of week 8. The OTR/up and OTR groups exhibited increased levels of BiP, pIRE-1 (Ser724), and pPERK (Thr981) in the hypothalamus at the end of week 8. There were no significant differences in the levels of caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) between the experimental groups at the end of week 8. In conclusion, the 3 overtraining protocols increased the endoplasmic reticulum stress at the end of week 8.

Keywords: apoptose; apoptosis; endoplasmic reticulum stress; hypothalamus; mice; overtrained by downhill running; overtraining protocols; protocoles de surentraînement; souris; stress dans le réticulum endoplasmique; surentraînement par course en pente négative.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers / metabolism
  • Blotting, Western
  • Cumulative Trauma Disorders / etiology
  • Cumulative Trauma Disorders / immunology
  • Cumulative Trauma Disorders / metabolism*
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress*
  • Heat-Shock Proteins / metabolism
  • Hypothalamus / enzymology
  • Hypothalamus / immunology
  • Hypothalamus / metabolism*
  • Male
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism*
  • Neurons / enzymology
  • Neurons / immunology
  • Neurons / metabolism*
  • Phosphorylation
  • Physical Conditioning, Animal / adverse effects*
  • Physical Exertion*
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism
  • Random Allocation
  • Unfolded Protein Response
  • eIF-2 Kinase / metabolism

Substances

  • Biomarkers
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Ern2 protein, mouse
  • PERK kinase
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase