Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse

Abstract

We used intact single fibres from a mouse foot muscle to study the role of oxidation‐reduction in the modulation of contractile function. The oxidant hydrogen peroxide (H2O2, 100‐300 μM) for brief periods did not change myoplasmic Ca2+ concentrations ([Ca2+]i) during submaximal tetani. However, force increased by 27 % during the same contractions. The effects of H2O2 were time dependent. Prolonged exposures resulted in increased resting and tetanic [Ca2+]i, while force was significantly diminished. The force decline was mainly due to reduced myofibrillar Ca2+ sensitivity. There was also evidence of altered sarcoplasmic reticulum (SR) function: passive Ca2+ leak was increased and Ca2+ uptake was decreased. The reductant dithiothreitol (DTT, 0.5‐1 mM) did not change tetanic [Ca2+]i, but decreased force by over 40 %. This was completely reversed by subsequent incubations with H2O2. The force decline induced by prolonged exposure to H2O2 was reversed by subsequent exposure to DTT. These results show that the elements of the contractile machinery are differentially responsive to changes in the oxidation‐reduction balance of the muscle fibres. Myofibrillar Ca2+ sensitivity appears to be especially susceptible, while the SR functions (Ca2+ leak and uptake) are less so.

Oxidative and proteolytic profiles of the right and left heart in a model of cancer-induced cardiac cachexia

“…Several studies have shown that these reactive species contribute to skeletal muscle dysfunction through different mechanisms. Brotto and Nosek [42] demonstrated a decrease in calcium release from the sarcoplasmic reticulum, and Andrade et al [43] demonstrated reduced sensitivity to calcium in muscles exposed to hydrogen peroxide. In addition, moderate oxidative stress has been reported to induce protein oxidation, with a consequent increase in intracellular proteolysis [45][46][47].…”

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

“…The sensitivity of a particular target is defined by the intrinsic sensitivity of the molecule to oxidation–reduction and the local redox state,103 and evidence has shown that RONS produced by skeletal muscle can alter myofilament structure and function 187. Several myofilament proteins including actin, α‐actinin,151, 187 troponin C188 and myosin heavy chains189, 190, 191 are susceptible to RONS‐induced oxidative modifications, thus affecting Ca 2+ dynamics and Ca 2+ sensitivity192 and, inevitably, cross‐bridge kinetics,188 which may result in contractile dysfunction.…”

Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals

“…Of many intracellular ROS production mechanisms, the mitochondrion is the most prominent ROS generator wherein constitutive ROS production arises from leakage of a small percent of electrons from the electron transfer chain (ETC) [7,8]. In skeletal muscle, which requires high energy supply and contains abundant mitochondria, adequate amount of ROS modulates muscle contractility and glucose metabolism [9,10], while excessive ROS is responsible for muscle fatigue and insulin resistance [1,11,12].…”