Endothelial CYB5R3 couples store-operated calcium entry to TRPV2 activation and vascular fitness.

ABSTRACT: NADH-cytochrome b5 reductase 3 (CYB5R3) is a flavoprotein that governs nitric oxide (NO) signaling and supports NADPH oxidase 4-derived hydrogen peroxide production via coenzyme Q reduction in endothelium. While CYB5R3 expression is decreased during aging, the downstream consequences of CYB5R3 loss are not understood. Here, we demonstrate that depletion of CYB5R3 in primary human aortic endothelial cells activates a Ca²⁺ influx network characterized by the upregulation of calcium release-activated calcium (CRAC) channel subunits ORAI2 and ORAI3, as well as the non-selective cation channel transient receptor potential vanilloid 2 (TRPV2). When endoplasmic-reticulum Ca²⁺ stores were depleted, CYB5R3-deficient cells had increased Ca²⁺ entry through the plasma

SUBMITTER: Katona M 

PROVIDER: S-EPMC12632602 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature