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.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Muscle Weakness/enzymology , Muscle, Skeletal/enzymology , Pulmonary Disease, Chronic Obstructive/enzymology , AMP-Activated Protein Kinases/genetics , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Disease Models, Animal , Down-Regulation , Gene Expression Regulation, Enzymologic , Male , Muscle Weakness/drug therapy , Muscle Weakness/genetics , Muscle Weakness/immunology , Muscle Weakness/pathology , Muscle, Skeletal/drug effects , Muscle, Skeletal/immunology , Muscle, Skeletal/pathology , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/pathology , RNA, Messenger/metabolism , Rats, Wistar , Resveratrol , Ribonucleotides/pharmacology , Sirtuin 1/metabolism , Stilbenes/pharmacology , Time Factors , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To investigate the impact of energy metabolism at the cellular level on the expression of the water channel protein aquaporin 1 (AQP1). METHODS: Balb/c mouse fibroblasts were incubated with iodoacetamide (IA) in vitro, and the changes in AQP1 expression were detected by immunoblotting and immunohistochemistry at 0, 4, and 6 h. RESULTS: IA induced the expression of AQP1 at 4 and 6 h accompanied with cell death. Reverse transcription PCR showed an increased expression of AQP1 mRNA in the cells. AQP1 expression was also upregulated by the inhibitor of microtubule and cytochrome C oxidase. CONCLUSION: A pretranslational regulation occurs in IA-induced AQP1 expression in mouse fibroblasts, and the up-regulated AQP1 accumulation is characterized by mitochondria-related energy dependence.
