Cooperative Interaction of trp Melastatin Channel Transient Receptor Potential (TRPM2) With Its Splice Variant TRPM2 Short Variant Is Essential for Endothelial Cell Apoptosis

• DOI: 10.1161/circresaha.114.302414
• Publication Date: 2013-12-12T02:27:30Z
• Authors: Claudie M. Hecquet; Min Zhang; Manish Mittal; Stephen M. Vogel; Anke Di; Xiaopei Gao; Marcelo G. Bonini; Asrar B. Malik
• Keywords: TRPM2

Rationale: Oxidants generated by activated endothelial cells are known to induce apoptosis, a pathogenic feature of vascular injury and inflammation from multiple pathogeneses. The melastatin-family transient receptor potential 2 (TRPM2) channel is an oxidant-sensitive Ca 2+ permeable implicated in mediating apoptosis; however, the mechanisms gating supranormal influx required for initiating apoptosis not understood. Objective: Here, we addressed role TRPM2 its interaction with short splice variant (TRPM2-S) entry burst induction cell apoptosis. Methods Results: We observed that TRPM2-S was basally associated plasmalemma, this functioned suppress TRPM2-dependent constitutively. Reactive oxygen species production or directly applying reactive induced protein kinase C-α activation phosphorylation at Ser 39. This turn stimulated large pathway. A similar mechanism seen intact vessels. C-α–activated phosphoswitch opened allow releasing inhibition TRPM2, which caspase-3 cleaved caspase substrate poly(ADP-ribose) polymerase. Conclusions: describe fundamental trp superfamily induces cells. signaling involves species–induced resulting allows enhanced TRPM2-mediated program. Strategies aimed preventing uncoupling subsequent during oxidative stress may mitigate consequences inflammation.