title: Activation of peroxisome proliferator-activated receptor-gamma during hepatic ischemia is age-dependent.
abstract: Hepatic ischemia/reperfusion injury is a complication of liver surgery, transplantation, and shock and is known to be age-dependent. Our laboratory has recently shown that peroxisome proliferator-activated receptor-gamma (PPARgamma) is down-regulated during hepatic ischemia and that this exacerbates injury. Here we examined whether activation of PPARgamma during ischemia was age-dependent. Male mice of different ages (young: 4-5 weeks; adult: 10-12 weeks; old: 10-12 months) were subjected to up to 90 min of hepatic ischemia. PPARgamma activation occurred throughout ischemia in young mice, whereas activation in adult and old mice was lost after 30 min. No significant differences were noted in PPARgamma ligand expression among the age groups. However, in young mice we observed a predominance of PPARgamma1 in the nucleus, whereas in old mice this isoform remained largely in the cytoplasm. Finally, the degree of PPARgamma activation was associated with autophagy in the liver, a mechanism of self-preservation. PPARgamma activation is prolonged in young mice as compared to older mice. This appears to be mediated by a selective retention of PPARgamma1 in the nucleus and is associated with increased autophagy. The data suggest that PPARgamma activation is an important component of the age-dependent response to hepatic ischemia/reperfusion injury.
authors.affiliation: The Laboratory of Trauma, Sepsis, and Inflammation Research, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Shin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuboki
authors.forename: Nadine
authors.initials: N
authors.lastname: Huber
authors.forename: Thorsten
authors.initials: T
authors.lastname: Eismann
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Galloway
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schuster
authors.forename: John
authors.initials: J
authors.lastname: Blanchard
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pritts
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
mesh_terms: D000367:Age Factors; D000818:Animals; D001343:Autophagy / Q000502:physiology; D007004:Hypoglycemic Agents; D007511:Ischemia / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones
chemical_list: D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone