Sirt1-ROS-TRAF6 Signaling-Induced Pyroptosis Contributes to Early Injury in Ischemic Mice

In this study, we evaluated the inflammatory reactions induced by acute ischemia and found that pyroptosis occurred after acute ischemia bothin vivo andin vitro, as determined by interleukin-1 β, apoptosis-associated speck-like protein, and caspase-1. The early inflammation resulted in irreversible ischemic injury, indicating that it deserves thorough investigation. Meanwhile, acute ischemia decreased the Sirtuin 1 (Sirt1) protein levels, and increased the TRAF6 (TNF receptor associated factor 6) protein and reactive oxygen species (ROS) levels. In further exploration, both Sirt1 suppression and TRAF6 activation were found to contribute to this pyroptosis. Reduced Sirt1 levels were responsible for the production of ROS and increased TRAF6 protein levels after ischemic exposure. Mor eover, N-acetyl-L-cysteine, an ROS scavenger, suppressed the TRAF6 accumulation induced by oxygen-glucose deprivationvia suppression of ROS bursts. These phenomena indicate that Sirt1 is upstream of ROS, and ROS bursts result in increased TRAF6 levels. Further, the activation of Sirt1 during the period of ischemia reduced ischemia-induced injury after 72  h of reperfusion in mice with middle cerebral artery occlusion. In sum, these results indicate that pyroptosis-dependent machinery contributes to the neural injury during acute ischemiavia the Sirt1-ROS-TRAF6 signaling pathway. We propose that inflammatory reactions occur soon after oxidative stress and are detrimental to neuronal survival; this...
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research