Abstract
The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis.
Highlights
The endoplasmic reticulum (ER) is a vital organelle in eukaryotic cells, responsible for multiple cellular activities, including synthesis, maturation, translation and folding of secretory and membrane proteins, lipid biogenesis, and the sequestration of Ca2+ [1,2]
This review focuses on: (a) ER stress and unfolded protein response (UPR) signal transduction pathways; (b) the role of Ca2+ in the ER stress and apoptosis; and (c) the involvement of action potential in ER stress-mediated apoptosis
Some studies have shown that the depletion of intracellular Ca2+ stores through the activation of Ryanodine receptors (RyRs) can induce apoptosis [132,133], because it leads to cytosolic Ca2+ overload, mitochondrial dysfunction, ER stress, and the subsequent cell death through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitotoxicity in oligodendrocytes [134]
Summary
The endoplasmic reticulum (ER) is a vital organelle in eukaryotic cells, responsible for multiple cellular activities, including synthesis, maturation, translation and folding of secretory and membrane proteins, lipid biogenesis, and the sequestration of Ca2+ [1,2]. Disturbances in the cellular energy levels, the redox state, or Ca2+ concentrations reduce the protein folding capacity of the ER, and lead to the accumulation and aggregation of unfolded proteins, resulting in ER stress [1]. Ca2+ is a major player in the regulation of cell death [18], both at the early and late stages of apoptosis, and severe Ca2+ dysregulation can induce ER stress-mediated apoptosis in response to various pathological conditions [19,20,21,22]. This review focuses on: (a) ER stress and UPR signal transduction pathways; (b) the role of Ca2+ in the ER stress and apoptosis; and (c) the involvement of action potential in ER stress-mediated apoptosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
