[Reduced expression of the sarcoplasmic calcium pump SERCA2 in skeletal muscle from patients with chronic obstructive pulmonary disease and low body weight]

Abstract

Objective: To compare the concentrations and extent of nitration of sarcoplasmic-endoplasmic reticulum Ca(2+) adenosine triphosphatase 2 (SERCA2) in biopsies of the quadriceps femoris from patients with chronic obstructive pulmonary disease (COPD) who have normal or low body mass index (BMI).

Patients and methods: The patients were divided into 2 groups (n=7, each group), one containing individuals with normal BMI (> 21 kg/m(2)) and the other with low BMI (< 21 kg/m(2)). Forced spirometry and blood gas analysis were performed in both groups and percutaneous needle biopsies of the lateral portion of the quadriceps femoris muscle were performed. Western blots were used to assess the concentration of SERCA2 in the biopsy material. To determine whether or not the protein was tyrosine-nitrated, immunoprecipitation of SERCA2 was performed with an antinitrotyrosine antibody followed by Western blotting to determine the concentration of the tyrosine-nitrated protein.

Results: Expression of SERCA2 was significantly lower in patients with low BMI (4.2 [0.5] vs 8.1 [1.2] integrated optical density units, P < .05). SERCA2 was also tyrosine-nitrated in the patients with low BMI. Finally, a significant negative correlation was observed between the concentration of SERCA2 and that of inducible nitric oxide synthase (determined in a previous study using the same biopsy material) in patients with COPD and low BMI (r=-0.89, P=.007), while such a correlation was not observed in patients with COPD and normal BMI (r=0.35, P=.43).

Conclusions: In patients with COPD, SERCA2 concentration is reduced and the protein is tyrosine-nitrated in skeletal muscle from patients with low BMI compared to those with normal BMI. These results indicate the presence of a previously unrecognized cellular alteration in skeletal muscle from patients with COPD and low muscle weight.