Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

Authors

  • Wei Yang 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
  • Britta Burkhardt Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany
  • Luise Fischer Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany
  • Maja Beirow Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany
  • Nadja Bork Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany
  • Eva C. Wönne Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus-Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
  • Cornelia Wagner Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany
  • Bettina Husen Pharmacelsus GmbH, Science Park 2, 66123 Saarbrücken, Germany
  • Katrin Zeilinger Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus-Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
  • Liegang Liu 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
  • Andreas K. Nussler Eberhard Karls University Tübingen, Dept. of Traumatology, Schnarrenbergstr. 95, 72076 Tübingen, Germany

DOI:

https://doi.org/10.17179/excli2015-734

Keywords:

aging, liver, antioxidant, Akt, MAPKs, cell proliferation

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 TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 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-eIF4ESer209 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.

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Published

2015-12-22

How to Cite

Yang, W., Burkhardt, B., Fischer, L., Beirow, M., Bork, N., Wönne, E. C., … Nussler, A. K. (2015). Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling. EXCLI Journal, 14, 1273–1290. https://doi.org/10.17179/excli2015-734

Issue

Vol. 14 (2015)

Section

Original articles

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