Calmodulin and Cyclic ADP-Ribose Interaction in Ca2+ Signaling Related to Cardiac Sarcoplasmic Reticulum: Superoxide Anion Radical-Triggered Ca2+ Release

Reactive oxygen species (ROS) are often shown to damage cellular functions. The targets of oxidative on the nature of ROS produced and the site of generation. In contrast, ROS can also regulate signal transduction. In this case, ROS may either induce or enhance events, which lead to forward directions of cellular signaling. The consequences of regulation of signal transduction can be observed in physiological processes such as muscle contraction. Here, we discuss the concentration-dependent effects of superoxide anion radical (center dot O-2(-)) on Ca2+ release from the cardiac sarcoplasmic reticulum (SR). Recent studies suggest that the ADP-ribosyl cyclase pathway, through its production of cyclic adenosine 5'-diphosphoribose (cADPR), may control Ca2+ mobilization in cardiac muscle cells. center dot O-2(-) has dual effects that are concentration dependent. At low concentrations (nearly nanomolar levels), center dot O-2(-) induces Ca2+ release by stimulating synthesis of cADPR, which requires calmodulin for sensitization of ryanodine-sensitive Ca2+-release channels (RyRC). At these low concentrations, center dot O-2(-) is responsible for regulation of cellular signal transduction. At higher concentrations (micromolar levels), center dot O-2(-) produces a loss in the function of calmodulin that is to inhibit RyRC. This results in an increase in Ca2+ release, which is linked to cell injury. The difference in the functions of low and high concentrations of center dot O-2(-) may result in two distinct physiological roles in cardiac muscle Ca2+ signaling. Antiox. Redox Signal. 2, 47-54.