Figure 8: Summary scheme of the mechanisms underlying NGR1’s inhibition on I/R-induced ERS and apoptosis.

I/R treatment induce the overexpression of GRP78 and accumulation of reactive oxygen species. The activation of GRP78 is able to induce a cascade of events that include the upregulation of ERS sensors ATF6, IRE1, and phosphorylation of PERK, resulting in the induction of apoptosis through CHOP, Caspase-12, and JNK-dependent pathways. NGR1 attenuate the up-regulated GRP78 expressions and inhibit the activation of ERS sensors, thus blocking the signalling pathways of ERS and their associated apoptosis. The inhibition of oxidative stress is relied on NGR1’s effects of scavenging free radical, abatementing the lipidperoxidament of cell membrane, and increasing the activity of antioxidase.