Differential expressions of antioxidant status in aging rats: the role of transcriptional factor Nrf2 and MAPK signaling pathway.
Antioxidant enzymes (AOEs) play an important role in the protection of cells against reactive oxygen species and facilitate the prevention of oxidative stress-induced aging. In the present study, the antioxidant indices, including the content of peroxidation product and the expression of AOEs in rat livers of varying ages (2, 12 and 18-24 months old) were evaluated. Erythrocytes haemolysis induced by free radicals showed significant age-dependent increases (P < 0.05). The content of oxidation products in livers showed that increasing age was associated with serious oxidative injury. The activities of AOEs decreased with increasing age. Expression of the antioxidant and age-related gene, klotho, decreased with increasing age. Western blot assay showed that aged rats experience higher levels of oxidative stress. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) exhibited an age-dependent decrease. Additionally, the mitogen-activated protein kinase cascade (MAPK) played a regulatory role in signaling transduction. Overall, we suggest that age-related declines of the antioxidant defense are closely involved with the expression of Nrf2 and are regulated by the MAPK family.
Shih
Ping-Hsiao
PH
Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan, Republic of China.
Yen
Gow-Chin
GC
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004912:Erythrocytes / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D006461:Hemolysis; D000090265:Klotho Proteins; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D050050:Protein Carbonylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D005980:Glutathione Reductase; D005966:Glucuronidase; D000090265:Klotho Proteins