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Inhibition of AMPK expression in skeletal muscle by systemic inflammation in COPD rats.

Qi Y, Shang JY, Ma LJ, Sun BB, Hu XG, Liu B, Zhang GJ - Respir. Res. (2014)

Bottom Line: Meanwhile, COPD also is associated with metabolic disorders, such as skeletal muscle weakness.Strikingly, activation of AMP-activated protein kinase (AMPK) exerts critical roles in energy metabolism.Such findings indicate that AMPK may serve as a target for therapeutic intervention in the treatment of muscle weakness in COPD patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital (He'nan Provincial People's Hospital), 7 Weiwu Road, ZhengZhou, 450003, China. rose20000@126.com.

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow limitation and inflammation. Meanwhile, COPD also is associated with metabolic disorders, such as skeletal muscle weakness. Strikingly, activation of AMP-activated protein kinase (AMPK) exerts critical roles in energy metabolism. However, it remains unclear whether and how the expression levels of AMPK are affected in the COPD model rats which may lead to the dysfunction of the skeletal muscle in these rats.

Methods: Here we developed a rat model of COPD, and we investigated the morphological changes of peripheral skeletal muscle and measured the levels of tumor necrosis factor -α (TNF-α) and AMPK in skeletal muscle by using approaches that include immunohistochemistry and polymerase chain reaction (PCR).

Results: We found that the expression levels of both AMPK mRNA and protein in skeletal muscles were significantly reduced in the COPD model rats, in comparison to those from the control rats, the COPD model rats that received treatments with AICAR and resveratrol, whereas the expression levels of TNF-α were elevated in COPD rats.

Conclusion: Such findings indicate that AMPK may serve as a target for therapeutic intervention in the treatment of muscle weakness in COPD patients.

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Related in: MedlinePlus

The expression of AMPK in muscle tissue was decreased in COPD model rats, and AICAR or resveratrol treatment recovered AMPK expression in COPD model rats. (A) Sample blots of AMPK and β-actin. Normalized muscle AMPK mRNA (B; Control: n = 14; COPD/saline: n = 12, 0.35 ± 0.04; COPD/AICAR, n = 14, 1.50 ± 0.12; COPD/Resveratrol, n = 12, 0.96 ± 0.05; ***F1, 25 = 68.31, p < 0.001 comparing the control group to the COPD/saline group; **F1, 27 = 11.89, p = 0.002 comparing the control group to the COPD/AICAR group; ###F1, 23 = 74.98, p < 0.001 comparing COPD/saline to COPD/resveratrol; ###F1, 25 = 60.98, p < 0.001 comparing COPD/saline to COPD/AICAR group). Normalized muscle AMPK protein (C; Control: n = 14; COPD/saline: n = 12, 0.32 ± 0.03; COPD/AICAR, n = 14, 0.96 ± 0.04; COPD/resveratrol, n = 12, 0.66 ± 0.01; ***F1, 25 = 66.17, p < 0.001 comparing the control group to the COPD/saline group; ***F1, 25 = 25.21, p < 0.001 comparing the control group to the COPD/resveratrol group; n.s. F1, 27 = 0.16, p = 0.70 comparing the control group to the COPD/AICAR; ###F1, 25 = 31.52, p < 0.001 comparing COPD/saline to COPD/AICAR; ###F1, 23 = 24.58, p < 0.001 comparing COPD/saline to COPD/resveratrol group. n.s. (not significant). Normalized muscle p-AMPK protein (D; Control: n = 6; COPD/saline: n = 6, 0.58 ± 0.14; COPD/AICAR, n = 6, 1.26 ± 0.30; COPD/resveratrol, n = 6, 1.29 ± 0.30; * F1, 11 = 5.1, p < 0.05 comparing the control group to the COPD/saline group; ###F2, 17 = 15.15, p < 0.001 comparing COPD/saline to COPD/AICAR and COPD/resveratrol. n.s. F2, 17 = 0.093 comparing the control group to the COPD/resveratrol group and COPD/resveratrol. n.s. (not significant).
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Fig6: The expression of AMPK in muscle tissue was decreased in COPD model rats, and AICAR or resveratrol treatment recovered AMPK expression in COPD model rats. (A) Sample blots of AMPK and β-actin. Normalized muscle AMPK mRNA (B; Control: n = 14; COPD/saline: n = 12, 0.35 ± 0.04; COPD/AICAR, n = 14, 1.50 ± 0.12; COPD/Resveratrol, n = 12, 0.96 ± 0.05; ***F1, 25 = 68.31, p < 0.001 comparing the control group to the COPD/saline group; **F1, 27 = 11.89, p = 0.002 comparing the control group to the COPD/AICAR group; ###F1, 23 = 74.98, p < 0.001 comparing COPD/saline to COPD/resveratrol; ###F1, 25 = 60.98, p < 0.001 comparing COPD/saline to COPD/AICAR group). Normalized muscle AMPK protein (C; Control: n = 14; COPD/saline: n = 12, 0.32 ± 0.03; COPD/AICAR, n = 14, 0.96 ± 0.04; COPD/resveratrol, n = 12, 0.66 ± 0.01; ***F1, 25 = 66.17, p < 0.001 comparing the control group to the COPD/saline group; ***F1, 25 = 25.21, p < 0.001 comparing the control group to the COPD/resveratrol group; n.s. F1, 27 = 0.16, p = 0.70 comparing the control group to the COPD/AICAR; ###F1, 25 = 31.52, p < 0.001 comparing COPD/saline to COPD/AICAR; ###F1, 23 = 24.58, p < 0.001 comparing COPD/saline to COPD/resveratrol group. n.s. (not significant). Normalized muscle p-AMPK protein (D; Control: n = 6; COPD/saline: n = 6, 0.58 ± 0.14; COPD/AICAR, n = 6, 1.26 ± 0.30; COPD/resveratrol, n = 6, 1.29 ± 0.30; * F1, 11 = 5.1, p < 0.05 comparing the control group to the COPD/saline group; ###F2, 17 = 15.15, p < 0.001 comparing COPD/saline to COPD/AICAR and COPD/resveratrol. n.s. F2, 17 = 0.093 comparing the control group to the COPD/resveratrol group and COPD/resveratrol. n.s. (not significant).

Mentions: Next, we examined if the expression levels of AMPK and p-AMPK were also affected in the COPD model rats, in according to that AMPK plays crucial functional roles in regulating energy metabolism [15]. We found that the expression levels of both AMPKα1 mRNA and protein in the skeletal muscle were significantly decreased in the COPD model rats, compared to those from the control rats and the COPD rats that were treated with AICAR and/or resveratrol (Figure 6A,B and C). As expected, the expression levels of the active p-AMPK were also significantly decreased in the COPD model rats and recovered with the treatment of AICAR and/or resveratrol (Figure 6D). We also noticed that the content of AMPKα protein in the resveratrol group was a little lower than that in the AICAR group (P <0.05), and further studies are needed to investigate the difference between them.Figure 6


Inhibition of AMPK expression in skeletal muscle by systemic inflammation in COPD rats.

Qi Y, Shang JY, Ma LJ, Sun BB, Hu XG, Liu B, Zhang GJ - Respir. Res. (2014)

The expression of AMPK in muscle tissue was decreased in COPD model rats, and AICAR or resveratrol treatment recovered AMPK expression in COPD model rats. (A) Sample blots of AMPK and β-actin. Normalized muscle AMPK mRNA (B; Control: n = 14; COPD/saline: n = 12, 0.35 ± 0.04; COPD/AICAR, n = 14, 1.50 ± 0.12; COPD/Resveratrol, n = 12, 0.96 ± 0.05; ***F1, 25 = 68.31, p < 0.001 comparing the control group to the COPD/saline group; **F1, 27 = 11.89, p = 0.002 comparing the control group to the COPD/AICAR group; ###F1, 23 = 74.98, p < 0.001 comparing COPD/saline to COPD/resveratrol; ###F1, 25 = 60.98, p < 0.001 comparing COPD/saline to COPD/AICAR group). Normalized muscle AMPK protein (C; Control: n = 14; COPD/saline: n = 12, 0.32 ± 0.03; COPD/AICAR, n = 14, 0.96 ± 0.04; COPD/resveratrol, n = 12, 0.66 ± 0.01; ***F1, 25 = 66.17, p < 0.001 comparing the control group to the COPD/saline group; ***F1, 25 = 25.21, p < 0.001 comparing the control group to the COPD/resveratrol group; n.s. F1, 27 = 0.16, p = 0.70 comparing the control group to the COPD/AICAR; ###F1, 25 = 31.52, p < 0.001 comparing COPD/saline to COPD/AICAR; ###F1, 23 = 24.58, p < 0.001 comparing COPD/saline to COPD/resveratrol group. n.s. (not significant). Normalized muscle p-AMPK protein (D; Control: n = 6; COPD/saline: n = 6, 0.58 ± 0.14; COPD/AICAR, n = 6, 1.26 ± 0.30; COPD/resveratrol, n = 6, 1.29 ± 0.30; * F1, 11 = 5.1, p < 0.05 comparing the control group to the COPD/saline group; ###F2, 17 = 15.15, p < 0.001 comparing COPD/saline to COPD/AICAR and COPD/resveratrol. n.s. F2, 17 = 0.093 comparing the control group to the COPD/resveratrol group and COPD/resveratrol. n.s. (not significant).
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Related In: Results  -  Collection

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Fig6: The expression of AMPK in muscle tissue was decreased in COPD model rats, and AICAR or resveratrol treatment recovered AMPK expression in COPD model rats. (A) Sample blots of AMPK and β-actin. Normalized muscle AMPK mRNA (B; Control: n = 14; COPD/saline: n = 12, 0.35 ± 0.04; COPD/AICAR, n = 14, 1.50 ± 0.12; COPD/Resveratrol, n = 12, 0.96 ± 0.05; ***F1, 25 = 68.31, p < 0.001 comparing the control group to the COPD/saline group; **F1, 27 = 11.89, p = 0.002 comparing the control group to the COPD/AICAR group; ###F1, 23 = 74.98, p < 0.001 comparing COPD/saline to COPD/resveratrol; ###F1, 25 = 60.98, p < 0.001 comparing COPD/saline to COPD/AICAR group). Normalized muscle AMPK protein (C; Control: n = 14; COPD/saline: n = 12, 0.32 ± 0.03; COPD/AICAR, n = 14, 0.96 ± 0.04; COPD/resveratrol, n = 12, 0.66 ± 0.01; ***F1, 25 = 66.17, p < 0.001 comparing the control group to the COPD/saline group; ***F1, 25 = 25.21, p < 0.001 comparing the control group to the COPD/resveratrol group; n.s. F1, 27 = 0.16, p = 0.70 comparing the control group to the COPD/AICAR; ###F1, 25 = 31.52, p < 0.001 comparing COPD/saline to COPD/AICAR; ###F1, 23 = 24.58, p < 0.001 comparing COPD/saline to COPD/resveratrol group. n.s. (not significant). Normalized muscle p-AMPK protein (D; Control: n = 6; COPD/saline: n = 6, 0.58 ± 0.14; COPD/AICAR, n = 6, 1.26 ± 0.30; COPD/resveratrol, n = 6, 1.29 ± 0.30; * F1, 11 = 5.1, p < 0.05 comparing the control group to the COPD/saline group; ###F2, 17 = 15.15, p < 0.001 comparing COPD/saline to COPD/AICAR and COPD/resveratrol. n.s. F2, 17 = 0.093 comparing the control group to the COPD/resveratrol group and COPD/resveratrol. n.s. (not significant).
Mentions: Next, we examined if the expression levels of AMPK and p-AMPK were also affected in the COPD model rats, in according to that AMPK plays crucial functional roles in regulating energy metabolism [15]. We found that the expression levels of both AMPKα1 mRNA and protein in the skeletal muscle were significantly decreased in the COPD model rats, compared to those from the control rats and the COPD rats that were treated with AICAR and/or resveratrol (Figure 6A,B and C). As expected, the expression levels of the active p-AMPK were also significantly decreased in the COPD model rats and recovered with the treatment of AICAR and/or resveratrol (Figure 6D). We also noticed that the content of AMPKα protein in the resveratrol group was a little lower than that in the AICAR group (P <0.05), and further studies are needed to investigate the difference between them.Figure 6

Bottom Line: Meanwhile, COPD also is associated with metabolic disorders, such as skeletal muscle weakness.Strikingly, activation of AMP-activated protein kinase (AMPK) exerts critical roles in energy metabolism.Such findings indicate that AMPK may serve as a target for therapeutic intervention in the treatment of muscle weakness in COPD patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital (He'nan Provincial People's Hospital), 7 Weiwu Road, ZhengZhou, 450003, China. rose20000@126.com.

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow limitation and inflammation. Meanwhile, COPD also is associated with metabolic disorders, such as skeletal muscle weakness. Strikingly, activation of AMP-activated protein kinase (AMPK) exerts critical roles in energy metabolism. However, it remains unclear whether and how the expression levels of AMPK are affected in the COPD model rats which may lead to the dysfunction of the skeletal muscle in these rats.

Methods: Here we developed a rat model of COPD, and we investigated the morphological changes of peripheral skeletal muscle and measured the levels of tumor necrosis factor -α (TNF-α) and AMPK in skeletal muscle by using approaches that include immunohistochemistry and polymerase chain reaction (PCR).

Results: We found that the expression levels of both AMPK mRNA and protein in skeletal muscles were significantly reduced in the COPD model rats, in comparison to those from the control rats, the COPD model rats that received treatments with AICAR and resveratrol, whereas the expression levels of TNF-α were elevated in COPD rats.

Conclusion: Such findings indicate that AMPK may serve as a target for therapeutic intervention in the treatment of muscle weakness in COPD patients.

Show MeSH
Related in: MedlinePlus