title: Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling.
abstract: Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2(Ser1254) decreased while ERK1/2 and TSC2(Thr1462) increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4E(Ser209) protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging.
authors.affiliation: Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany; Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Burkhardt
authors.affiliation: Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany.
authors.forename: Luise
authors.initials: L
authors.lastname: Fischer
authors.affiliation: Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Beirow
authors.affiliation: Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Bork
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus-Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Wönne
authors.affiliation: Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Wagner
authors.affiliation: Pharmacelsus GmbH, Science Park 2, 66123 Saarbrücken, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Husen
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus-Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Zeilinger
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
authors.forename: Liegang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Nussler
keywords: Akt; MAPKs; aging; antioxidant; cell proliferation; liver