Korean J Physiol Pharmacol.  2014 Jun;18(3):211-216. 10.4196/kjpp.2014.18.3.211.

Effect of Exercise Intensity on Unfolded Protein Response in Skeletal Muscle of Rat

• Kim K
• Kim YH
• Lee SH
• Jeon MJ
• Park SY
• Doh KO

• KMID: 2285512
• DOI: http://doi.org/10.4196/kjpp.2014.18.3.211

Abstract

Endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and mitochondrial biogenesis were assessed following varying intensities of exercise training. The animals were randomly assigned to receive either low- (LIT, n=7) or high intensity training (HIT, n=7), or were assigned to a control group (n=7). Over 5 weeks, the animals in the LIT were exercised on a treadmill with a 10degrees incline for 60 min at a speed of 20 m/min group, and in the HIT group at a speed of 34 m/min for 5 days a week. No statistically significant differences were found in the body weight, plasma triglyceride, and total cholesterol levels across the three groups, but fasting glucose and insulin levels were significantly lower in the exercise-trained groups. Additionally, no statistically significant differences were observed in the levels of PERK phosphorylation in skeletal muscles between the three groups. However, compared to the control and LIT groups, the level of BiP was lower in the HIT group. Compared to the control group, the levels of ATF4 in skeletal muscles and CHOP were significantly lower in the HIT group. The HIT group also showed increased PGC-1alpha mRNA expression in comparison with the control group. Furthermore, both of the trained groups showed higher levels of mitochondrial UCP3 than the control group. In summary, we found that a 5-week high-intensity exercise training routine resulted in increased mitochondrial biogenesis and decreased ER stress and apoptotic signaling in the skeletal muscle tissue of rats.

Keyword

ER stress; Exercise; Mitochondria; Skeletal muscle; Unfolded protein responses

MeSH Terms

Animals
Body Weight
Cholesterol
Endoplasmic Reticulum
Fasting
Glucose
Insulin
Mitochondria
Organelle Biogenesis
Muscle, Skeletal*
Phosphorylation
Plasma
Rats*
RNA, Messenger
Triglycerides
Unfolded Protein Response*
Cholesterol
Glucose
Insulin
RNA, Messenger

Figure

• 

  Fig. 1 The effects of high- and low-intensity exercise training on ER stress and the unfolded protein response pathway in the skeletal muscle tissue of rats. (A) Phosphorylation of PERK and (B) BiP were analyzed by western blotting in trained (LIT and HIT) and control rats. GAPDH was used as a control to ensure equal protein loading. Protein density was measured and represented in arbitrary units. Gene expression of ATF3 (C) and ATF4 (D) were analyzed using real-time PCR. Error bars represent the mean±SEM of six rats. *p<0.05 vs. Control, #p<0.05 vs. LIT or HIT (A. U., arbitrary unit; ATF, activating transcription factor; BiP, immunoglobulin heavy chain-binding protein; CON, control group; ER, endoplasmic reticulum; HIT, high-intensity training group; LIT, low-intensity training group; PERK, protein kinase RNA-like ER kinase; pPERK, phosphorylated PERK).

• 

  Fig. 2 The effect of high- and low-intensity exercise training on CHOP in the skeletal muscle tissue of rats. Gene expression (A) and protein level (B) were analyzed using real-time PCR and western blotting in trained (LIT and HIT) and control rats. GAPDH was used as a control to ensure equal protein loading. mRNA and protein density were measured and represented in arbitrary units. Gene expression of CHOP was normalized by the expression of GAPDH. Error bars represent the mean±SEM of six rats. *p<0.05 vs. Control, #p<0.05 vs LIT or HIT (A. U., arbitrary unit; CHOP, C/EBP-homologous protein; CON, control group; HIT, high-intensity training group; LIT, low-intensity training group).

• 

  Fig. 3 Mitochondrial gene expression following high- and low-intensity exercise training in the skeletal muscle tissue of rats. Gene expression of PGC-1α (A) and UCP3 (B) were analyzed using real-time PCR in trained (LIT and HIT) and control rats. GAPDH was used as a control to ensure equal protein loading. Protein density was measured and represented in arbitrary units. Mitochondrial gene expression was normalized by the expression of GAPDH. Error bars represent the mean±SEM of six rats. *p<0.05 vs. Control (A. U., arbitrary unit; CON, control group; HIT, high-intensity training group; LIT, low-intensity training group; PGC-1α, peroxisome proliferator-activator receptor gamma coactivator-1 alpha; UCP3, mitochondrial uncoupling protein 3).

• 

  Fig. 4 A model of decreased ER stress following exercise training (ATF, activating transcription factor; BiP, immunoglobulin heavy chain-binding protein; CHOP, C/EBP-homologous protein; ER, endoplasmic reticulum; PGC-1α, peroxisome proliferator-activator receptor gamma coactivator-1 alpha).

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