Cardioprotection of ischaemic preconditioning is associated with inhibition of translocation of MLKL within the plasma membrane.

Cardioprotection of ischaemic preconditioning is associated with inhibition of translocation of MLKL within the plasma membrane. J Cell Mol Med. 2018 Jun 19;: Authors: Szobi A, Farkašová-Ledvényiová V, Lichý M, Muráriková M, Čarnická S, Ravingerová T, Adameová A Abstract Necroptosis, a form of cell loss involving the RIP1-RIP3-MLKL axis, has been identified in cardiac pathologies while its inhibition is cardioprotective. We investigated whether the improvement of heart function because of ischaemic preconditioning is associated with mitigation of necroptotic signaling, and these effects were compared with a pharmacological antinecroptotic approach targeting RIP1. Langendorff-perfused rat hearts were subjected to ischaemic preconditioning with or without a RIP1 inhibitor (Nec-1s). Necroptotic signaling and the assessment of oxidative damage and a putative involvement of CaMKII in this process were analysed in whole tissue and subcellular fractions. Ischaemic preconditioning, Nec-1s and their combination improved postischaemic heart function recovery and reduced infarct size to a similar degree what was in line with the prevention of MLKL oligomerization and translocation to the membrane. On the other hand, membrane peroxidation and apoptosis were unchanged by either approach. Ischaemic preconditioning failed to ameliorate ischaemia-reperfusion-induced increase in RIP1 and RIP3 while pSer229-RIP3 levels were reduced only by ...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research