Emerging roles of Orai3 in pathophysiology

Leukotriene-C4 Synthase, a Critical Enzyme in the Activation of Store-independent Orai1/Orai3 Channels, Is Required for Neointimal Hyperplasia

“…More specifically, our laboratory has recently reported a novel role for LTC 4 in VSMCs distinct from its known proinflammatory capabilities. We showed that intracellular LTC 4 in VSMCs could mediate Ca 2ϩ entry across the plasma membrane through a store-independent pathway contributed by a heteromultimeric Orai1/Orai3 channel and regulated by the Ca 2ϩ sensor STIM1 (13)(14)(15)(16)(17). Previous studies from our group and others have demonstrated the up-regulation of STIM1, Orai1, and Orai3 in synthetic cultured VSMCs and medial and neointimal VSMCs after vascular injury.…”

Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury

“…Orai1 expression was also observed in CD8 + , B cells, NK cells, and macrophages but the percentage of these populations was modest when compared with CD4 + cells (Supplemental Table 2; supplemental material available online with this article; https://doi.org/10.1172/JCI126108DS1). Orai1 has 2 homologs, referred to Orai2 and Orai3, which have been suggested to modulate lymphocyte responses (19,20). However, neither Orai2 nor Orai3 was significantly affected by I/R and neither Orai2 + nor Oria3 + cells coexpressed IL-17 (Supplemental Figure 2).…”

Cisplatin (CDDP) triggers cell death of MCF-7 cells following disruption of intracellular calcium ([Ca²⁺]_i) homeostasis

“…kinases and calmodulin) have different cellular and tissue distribution and their regulation occur through multiple signaling pathways (Monteith et al, 2007). Deregulation of calcium homeostasis has been reported in a wide variety of pathological conditions including cardiovascular disorders, cancer and neurodegenerative diseases (Motiani et al, 2013). In recent years it has been emphasized that cancers are associated with alterations in specific Ca 2+ channels or pumps (e.g.…”