caa a22 4500 606236708 CHVBK 20210128101249.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s11010-015-2358-6 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2358-6 Fibroblast growth factor (FGF21) protects mouse liver against d -galactose-induced oxidative stress and apoptosis via activating Nrf2 and PI3K/Akt pathways [Elektronische Daten] [Yinhang Yu, Fuliang Bai, Yaonan Liu, Yongbi Yang, Qingyan Yuan, Dehua Zou, Susu Qu, Guiyou Tian, Liying Song, Tong Zhang, Siming Li, YunYe Liu, Wenfei Wang, Guiping Ren, Deshan Li] FGF21 is recently discovered with pleiotropic effects on glucose and lipid metabolism. However, the potential protective effect of FGF21 against d-gal-induced injury in the liver has not been demonstrated. The aim of this study is to investigate the pathophysiological role of FGF21 on hepatic oxidative injury and apoptosis in mice induced by d-gal. The 3-month-old Kunming mice were subcutaneously injected with d-gal (180mgkg−1d−1) for 8weeks and administered simultaneously with FGF21 (5 or 1mgkg−1d−1). Our results showed that the administration of FGF21 significantly alleviated histological lesion including structure damage, degeneration, and necrosis of hepatocytes induced by d-gal, and attenuated the elevation of liver injury markers, serum AST, and ALP in a dose-dependent manner. FGF21 treatment also suppressed d-gal-induced profound elevation of ROS production and oxidative stress, as evidenced by an increase of the MDA level and depletion of the intracellular GSH level in the liver, and restored the activities of antioxidant enzymes SOD, CAT, GSH-Px, and T-AOC. Moreover, FGF21 treatment increased the nuclear abundance of Nrf2 and subsequent up regulation of several antioxidant genes. Furthermore, a TUNEL assay showed that d-gal-induced apoptosis in the mouse liver was significantly inhibited by FGF21. The expression of caspase-3 was markedly inhibited by the treatment of FGF21 in the liver of d-gal-treated mice. The levels of PI3K and PBK/Akt were also largely enhanced, which in turn inactivated pro-apoptotic signaling events, restoring the balance between pro- and anti-apoptotic Bcl-2 and Bax proteins in the liver of d-gal-treated mice. In conclusion, these results suggest that FGF21 protects the mouse liver against d-gal-induced hepatocyte oxidative stress via enhancing Nrf2-mediated antioxidant capacity and apoptosis via activating PI3K/Akt pathway. Springer Science+Business Media New York, 2015 FGF21 nationallicence d -Gal nationallicence Nrf2-mediated antioxidant capacity nationallicence PI3K/AKT nationallicence Apoptosis nationallicence FGF21 : Fibroblast growth factor 21 nationallicence d -Gal : d-Galactose nationallicence AST : Aspartate aminotransferase nationallicence ALP : Alkaline phosphatase nationallicence ROS : Reactive oxygen species nationallicence MDA : Malondialdehyde nationallicence GSH : Glutathione nationallicence SOD : Superoxide dismutase nationallicence CAT : Catalase nationallicence GSH-Px : Glutathione peroxidase nationallicence T-AOC : Total antioxidation capability nationallicence Nrf2 : Nuclear factor erythroid 2-related factor 2 nationallicence TUNEL : Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling nationallicence PI3K : Phosphoinositide-3-kinase nationallicence PBK/Akt : Protein kinase B nationallicence Yu Yinhang Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Bai Fuliang Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Liu Yaonan Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Yang Yongbi Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Yuan Qingyan Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Zou Dehua Heilongjiang Bayi Agricultural University, 163319, Daqing, China aut Qu Susu Institute of Psychology, Chinese Academy of Sciences, 100101, Beijing, China aut Tian Guiyou Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Song Liying Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Zhang Tong Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Li Siming Harbin University of Commerce, 150028, Harbin, China aut Liu YunYe Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Wang Wenfei Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Ren Guiping Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Li Deshan Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 287-299 0300-8177 403:1-2<287 2015 403 11010 https://doi.org/10.1007/s11010-015-2358-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2358-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yu Yinhang Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Bai Fuliang Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Liu Yaonan Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Yang Yongbi Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Yuan Qingyan Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Zou Dehua Heilongjiang Bayi Agricultural University, 163319, Daqing, China aut NATIONALLICENCE 700 1- Qu Susu Institute of Psychology, Chinese Academy of Sciences, 100101, Beijing, China aut NATIONALLICENCE 700 1- Tian Guiyou Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Song Liying Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Zhang Tong Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Li Siming Harbin University of Commerce, 150028, Harbin, China aut NATIONALLICENCE 700 1- Liu YunYe Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Wang Wenfei Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Ren Guiping Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 700 1- Li Deshan Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, 150030, Harbin, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 287-299 0300-8177 403:1-2<287 2015 403 11010