Relationships among stress responses and cell apoptosis and necrosis

Earlier models of stress reactions did not consider the concurrent coupling of intracellular Ca²⁺ levels with the concomitant release of ATP and the production of reactive oxygen species (ROS). In such conditions, extracellular ATP acting on purinergic type 2 (P2) receptors can trigger the release of various mediator molecules that support cellular defence. Additionally, extracellular adenosine (Ado), formed from ATP, acts on P1 receptors to moderate and control mediator release, preventing cellular hyperactivity, supporting survival, replenishing ATP pools, or, in certain cases, inducing a pathological state. In this study, we present three integrated models, based on earlier publications and complemented by new original observations: a) “Model of the extracellular ATP–adenosine danger cycle coupled to stress hormones”; b) “Model of cellular homeostasis, apoptosis, and necrosis in various danger/stress situations related to Ca²⁺, ATP, and adenosine”; c) “Model of intracellular, extracellular, and systemic elements of stress responses related to the ATP-adenosine danger cycle, ROS, and hormones.”