Purinergic signaling promotes premature senescence.

ABSTRACT: Extracellular ATP activates P2 purinergic receptors. Whether purinergic signaling is functionally coupled to cellular senescence is largely unknown. We find that oxidative stress induced release of ATP and caused senescence in human lung fibroblasts. Inhibition of P2 receptors limited oxidative stress-induced senescence, while stimulation with exogenous ATP promoted premature senescence. Pharmacological inhibition of P2Y11 receptor (P2Y11R) inhibited premature senescence induced by either oxidative stress or ATP, while stimulation with a P2Y11R agonist was sufficient to induce cellular senescence. Our data show that both extracellular ATP and a P2Y11R agonist induced calcium (Ca⁺⁺) release from the endoplasmic reticulum (ER) and that either inhibition of phospholipase C or intra

SUBMITTER: Volonte D 

PROVIDER: S-EPMC11002311 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature