Activation of Peroxisome Proliferator-Activated Receptor-γ During Hepatic Ischemia Is Age-Dependent

Abstract

Hepatic ischemia/reperfusion (I/R) injury is a complication of liver surgery, transplantation and shock and is known to be age-dependent. Our laboratory has recently shown that peroxisome proliferatoractivated receptor-gamma (PPARγ) is downregulated during hepatic ischemia and that this exacerbates injury. Here we examined whether activation of PPARγ during ischemia was agedependent. Male mice of different ages (young: 4-5 weeks; adult: 10-12 weeks; old: 10-12 months) were subjected to up to 90 minutes of hepatic ischemia. PPARγ activation occurred throughout ischemia in young mice, whereas activation in adult and old mice was lost after 30 minutes. No significant differences were noted in PPARγ ligand expression amongst the age groups. However, in young mice we observed a predominance of PPARγ1 in the nucleus, whereas in old mice this isoform remained largely in the cytoplasm. Finally, the degree of PPARγ activation was associated with autophagy in the liver, a mechanism of self-preservation.Conclusion-PPARγ activation is prolonged in young mice as compared to older mice. This appears to be mediated by a selective retention of PPARγ1 in the nucleus and is associated with increased autophagy. The data suggest that PPARγ activation is an important component of the agedependent response to hepatic I/R injury.

Liver apoptosis is age dependent and is reduced by activation of peroxisome proliferator-activated receptor-γ in hemorrhagic shock

“…In contrast, the marked decrease of PPAR␥ in the lung of mature rats hampers the ability of specific ligands to enable efficient DNA binding of PPAR␥ (39). In support to our hypothesis, Shin et al (29) have previously reported that, in the liver of old mice following hepatic ischemia and reperfusion, loss of the nuclear expression of the isoform PPAR␥1 is secondary to the receptor retention in the cytosol and treatment with the specific ligand rosiglitazone increases its nuclear translocation. Thus taken together these data suggest that constitutive activation of the receptor may exhibit a tissue specific pattern in the mature rats and may depend on the metabolic organ function.…”

Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

“…Hepatic ischemia and reperfusion injury is observed following major liver surgery, transplantation, trauma and sepsis and may cause metabolic and structural hepatic damage [25,26] . This remains a significant problem in surgical procedures, and is a limitation of liver transplantation [27] .…”

Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

“…Ischemia followed by reperfusion (I/R) may cause metabolic and structural hepatic damage, and may be due to trauma, sepsis, liver transplantation [1] or hepatic pedicle clamping during liver surgery [2] . This remains a significant problem for surgical procedures, and also remains limitation of liver transplantation [3] .…”