Redox Regulation of Store-Operated Ca²⁺Entry

Abstract

Significance: Store-operated Ca 2+ entry (SOCE) is a ubiquitous Ca 2+ signaling mechanism triggered by Ca 2+ depletion of the endoplasmic reticulum (ER) and by a variety of cellular stresses. Reactive oxygen species (ROS) are often concomitantly produced in response to these stresses, however, the relationship between redox signaling and SOCE is not completely understood. Various cardiovascular, neurological, and immune diseases are associated with alterations in both Ca 2+ signaling and ROS production, and thus understanding this relationship has therapeutic implications. Recent Advances: Several reactive cysteine modifications in stromal interaction molecule (STIM) and Orai proteins comprising the core SOCE machinery were recently shown to modulate SOCE in a redox-dependent manner. Moreover, STIM1 and Orai1 expression levels may reciprocally regulate and be affected by responses to oxidative stress. ER proteins involved in oxidative protein folding have gained increased recognition as important sources of ROS, and the recent discovery of their accumulation in contact sites between the ER and mitochondria provides a further link between ROS production and intracellular Ca 2+ handling. Critical Issues and Future Directions: Future research should aim to establish the complete set of SOCE controlling molecules, to determine their redox-sensitive residues, and to understand how intracellular Ca 2+ stores dynamically respond to different types of stress. Mapping the precise nature and functional consequence of key redox-sensitive components of the pre-and post-translational control of SOCE machinery and of proteins regulating ER calcium content will be pivotal in advancing our understanding of the complex crosstalk between redox and Ca 2+ signaling. Antioxid. Redox Signal. 21, 915-932.

Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

“…But, whether ginsenoside Rb1 acts directly through interactions with STIM1, TRPC1 and Orai1, or indirectly through other signaling pathways is unclear. Recent evidence has indicated that SOCE can be regulated by reactive oxygen species (ROS) through redox-dependent modification of STIM and Orai proteins [57]. Since ginsenoside Rb1 is known to reduce oxidative stress in different cells and tissues [17,27,58,59], it is possible that it modulates SOCE through a ROS-related mechanism.…”

Redox regulation of T-cell receptor signaling

“…For more details regarding redox regulation of ion channels in different immune and non-immune cell types we recommend the following literature: Bogeski et al (2011);Takahashi et al (2011);Bogeski and Niemeyer (2014); O-Uchi et al (2014a, b); Kozai et al (2014); Nunes and Demaurex (2014); Paula-Lima et al (2014); Sahoo et al (2014); Stojilkovic et al (2014); Todorovic and Jevtovic-Todorovic (2014).…”

Prion Protein Signaling in the Nervous System—A Review and Perspective

“…There would also likely be an accompaniment of activation on TRPV 1 , a redox sensor responding to increased ROS 196 and store-operated Ca 2+ entry. 197 This mechanism is important in the acute synovial inflammation that results in TRPV 1 -mediated cell destruction 198 and points to a role of PrP C in modulating inflammatory joint disease. PrP C and body symmetry.…”