1. Recent insights on the mechanisms of liver preconditioning
Rita Carini, Emanuele Albano 
Gastroenterology 
Volume 125, Issue 5, Pages (November 2003)
DOI: /j.gastro

2. Figure 1
Proposed mechanisms leading to the development of hepatocyte resistance to ischemia/reperfusion injury following early hepatic preconditioning. The stimulation by adenosine of adenosine A2A receptors induces a network of signals involving Gi proteins, phospholipase C (PLC), and PI3-K that mediates the sequential activation of PKC (PKC-δ and PKC-ϵ) and p38 MAPK. NO released by endothelial NO synthase can also stimulate p38 MAPK through the activation of soluble guanylate cyclase (cG-S) and cGK. The signals transduced by p38 MAPK, PKB/Akt, and AMP-dependent kinase (AMPK) can activate a variety of mechanisms (dotted lines) able to preserve energy sources, mitochondrial functions, pH, and ion homeostasis as well as to reduce oxidative injury and caspase activation. The combination of these effects decreases liver cell susceptibility to necrosis and/or apoptosis in response to ischemia/reperfusion.
Gastroenterology  , DOI: ( /j.gastro )

3. Figure 2
Modulation of inflammatory response by hepatic preconditioning. Preconditioning stimuli reduce the expression by sinusoidal endothelial cells of leukocyte adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin), decreasing postischemic neutrophil infiltration of the liver. Preconditioning also attenuates the production of reactive oxygen species, TNF-α, and CXC chemokines by Kupffer cells and reduces endothelin secretion by endothelial cells, ameliorating sinusoidal perfusion and microvascular dysfunction. The effect of preconditioning on TNF-α release decreases the up-regulation of P-selectin in the lungs and splanchnic organs, protecting against systemic inflammatory disorders associated with hepatic ischemia/reperfusion. XDH, xanthine dehydrogenase; XOD, xanthine oxidase.
Gastroenterology  , DOI: ( /j.gastro )

4. Figure 3
Proposed mechanisms in the development of late hepatic preconditioning. The cellular signals that induce late hepatic preconditioning are still largely uncharacterized. It is possible that NF-κB and p38 MAPK-regulated transcription factors (ATF-2 and MEF2C) might be responsible for inducing the expression of protective genes, including Mn-superoxide dismutase (SOD-2), and inducible NO synthase (iNOS) as well as by stimulating the expression of cycline D1. Preconditioning signals also activate heat shock transcription factor 1 (HSF1), and its binding to specific heat shock recognition sequences (HSE) in the DNA leads to the production of HSP27, HSP70, and HO-1/HSP32. The binding of HSPs to cytochrome c, APAF-1, and AIF might be involved in preventing apoptosis, whereas HO-1-catalyzed conversion of heme into biliverdin and bilirubin increases cellular antioxidant defenses. It is also possible that HSPs might contribute to improve membrane potential and respiratory control in hepatic mitochondria, allowing a faster recovery of ATP on reoxygenation.
Gastroenterology  , DOI: ( /j.gastro )