Fig. 2.

Reperfusion Injury Salvage Kinase (RISK) and Survivor Activating Factor Enhancement (SAFE) pathway model of ischaemic conditioning. The acute ischaemic stress of non-injurious ischaemia leads to the release of multiple stress-inducible factors that may activate through G-protein coupled receptors (GCPR) or receptor tyrosine kinases (RTK) to induce the RISK cascade, or through inflammatory cytokines via the glycoprotein 130 (gp130) or tumour necrosis factor receptor (TNFR) to activate the SAFE pathway. The resulting signalling cascade then impacts upon mitochondria, potentially inhibiting the mitochondrial permeability transition pore (mPTP) and other mitochondrial proteins such as connexin-43 (Cx43), or via the nucleus to induce, through promotors, new protein synthesis. PI3K (Phosphoinositide 3-kinase), Akt [Serine/threonine kinase (protein kinase B)], eNOS (Endothelial nitric oxide synthase), ERK (Extracellular signal-regulated kinases), JAK (Janus Kinase), MEK (Mitogen-activated protein kinase kinase), NO (Nitric oxide), p70S6K (p70 S6 ribosomal protein kinase), PKC (Protein Kinase C), Ras/Raf (small GTPase proteins), STAT (Signal transducer and activator of transcription)