喫煙は、呼吸筋障害より先行して、直接、筋肉量減少・機能低下をもたらす

内科開業医のお勉強日記ブログからの引用です。COPDは単なる呼吸器疾患ではなく、筋障害も生じる全身性疾患であるという仮説を検証した論文の1つです。サルコペニアの予防と治療にも、COPDでなくても禁煙は必要といえます。

喫煙は、呼吸筋障害より先行して、直接、筋肉量減少・機能低下をもたらす
http://intmed.exblog.jp/11141631/

喫煙による筋肉の影響は、呼吸器系障害から筋肉へ影響を与えるより前に、筋肉の蛋白にoxidative damageを与え、これが筋肉の減少・機能低下をもたらしている。

すなわち、ＣＯＰＤは、”喫煙が原因による、筋肉・呼吸器系を含む全身性疾患”である。

Cigarette Smoke–induced Oxidative Stress
A Role in Chronic Obstructive Pulmonary Disease Skeletal Muscle Dysfunction
American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 477-488, (2010) ENIGMA in COPD Project

解糖系酵素、クレアチニンキナーゼ、炭酸脱水酵素（carbonic anydrase-3）、筋収縮蛋白が有意に喫煙者・ＣＯＰＤ患者で、カルボニル化されている。喫煙暴露モルモットでも呼吸筋・四肢筋で確認。

心理的要素がこれに加わると主のだが・・・

細胞や組織で発生する活性酸素種（ROS）は近くに存在するタンパク質を非特異的に酸化します。タンパク質の酸化修飾体として、よく知られているのがカルボニル化タンパク質です。カルボニル化タンパク質はタンパク質中のプロリン、アルギニン、リシン、スレオニンなどのアミノ酸がROSにより酸化修飾を受け、カルボニル誘導体となったタンパク質の総称です。カルボニル誘導体は化学的に安定なため、近年、典型的な酸化ストレスのマーカーとして頻繁に用いられています。(解説借用)

Rationale: Inflammation and oxidative stress contribute to muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). Oxidants contained in cigarette smoke (CS) induce adverse effects on tissues through oxidative phenomena.

Objectives: To explore oxidative stress and inflammation in quadriceps of human smokers and in diaphragm and limb muscles of guinea pigs chronically exposed to CS.

Methods: Muscle function, protein oxidation and nitration, antioxidants, oxidized proteins, inflammation, creatine kinase activity, and lung and muscle structures were investigated in vastus lateralis of smokers, patients with COPD, and healthy control subjects and in diaphragm and gastrocnemius of CS-exposed guinea pigs at 3, 4, and 6 months.

Measurements and Main Results: Compared with control subjects, quadriceps muscle force was mildly but significantly reduced in smokers; protein oxidation levels were increased in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed animals; glycolytic enzymes, creatine kinase, carbonic anydrase-3, and contractile proteins were significantly more carbonylated in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed guinea pigs. Chronic CS exposure induced no significant rise in muscle inflammation in either smokers or rodents. Muscle creatine kinase activity was reduced only in patients with COPD and in both diaphragm and gastrocnemius of CS-exposed animals. Guinea pigs developed bronchiolar abnormalities at 4 months of exposure and thereafter.

Conclusions: CS exerts direct oxidative modifications on muscle proteins, without inducing any significant rise in muscle inflammation. The oxidative damage to muscle proteins, which precedes the characteristic respiratory changes, may contribute to muscle loss and dysfunction in smokers and patients with COPD.

AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject
Oxidative stress is a proposed contributor to chronic obstructive pulmonary disease (COPD) muscle dysfunction. Oxidants contained in cigarette smoke induce adverse effects on tissues through oxidative modifications of key biological structures. It remains to be elucidated whether chronic cigarette smoking induces direct oxidative damage in skeletal muscles.

What This Study Adds to the Field
Chronic cigarette smoking exerts direct oxidative modifications on muscle proteins, without inducing significant rise in either molecular or cellular muscle inflammation. Importantly, the oxidative damage to specific muscle proteins, which precedes the characteristic respiratory changes, may contribute to muscle mass loss and dysfunction in smokers and patients with COPD.