The FASEB journal, 2019-07, Vol.33 (7), p.8022-8032
2019
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Details
- Autor(en) / Beteiligte
- Titel
- p62/SQSTM1 and Nrf2 are essential for exercise‐mediated enhancement of antioxidant protein expression in oxidative muscle
- Ist Teil von
- The FASEB journal, 2019-07, Vol.33 (7), p.8022-8032
- Ort / Verlag
- United States: Federation of American Societies for Experimental Biology
- Erscheinungsjahr
- 2019
- Quelle
- Wiley Online Library Journals Frontfile Complete
- Beschreibungen/Notizen
- ABSTRACT Increased muscle contractile activity, as observed with regular exercise, prevents oxidative stress—induced muscle wasting, at least partially, by improving the antioxidant defense system. Phosphorylated p62/sequestosome1 competitively binds to the Kelch‐like ECH‐associated protein 1, activating nuclear factor erythroid 2—related factor 2 (Nrf2), which stimulates transcription of antioxidant/electrophile responsive elements. However, it remains to be determined if this process is activated by regular exercise in skeletal muscle. Here, we demonstrate that muscle contractile activity increases antioxidants, Nrf2 translocation into nuclei, and Nrf2 DNA‐binding activity in association with increased p62 phosphorylation (Ser351) in mouse oxidative skeletal muscle. Skeletal muscle‐specific loss of Nrf2 [i.e., Nrf2 muscle‐specific knockout (mKO) mice] abolished the expression of the Nrf2 target antioxidant gene NAD(P)H‐quinone oxidoreductase 1 (NQO1) in both glycolytic and oxidative muscles but reduced exercise‐mediated increases of antioxidants (i.e., copper/zinc superoxide dismutase (SOD) and extracellular SOD only in oxidative muscle. Interestingly, skeletal muscle—specific loss of p62 (i.e., p62 mKO mice) also abolished the expression of NQO1 and reduced exercise‐mediated increases of the same antioxidants in soleus muscle. Collectively, these findings indicate that p62 and Nrf2 cooperatively regulate the exercise‐mediated increase of antioxidants in oxidative muscle.—Yamada, M., Iwata, M., Warabi, E., Oishi, H., Lira, V. A., Okutsu, M. p62/SQSTM1 and Nrf2 are essential for exercise‐mediated enhancement of antioxidant protein expression in oxidative muscle. FASEB J. 33, 8022–8032 (2019). www.fasebj.org
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0892-6638eISSN: 1530-6860DOI: 10.1096/fj.201900133RTitel-ID: cdi_proquest_miscellaneous_2198565374
- Format
- –
- Schlagworte
- Animals, Cell Nucleus - enzymology, Cells, Cultured, CuZnSOD, Cytoplasm - enzymology, EcSOD, Glycolysis, glycolytic skeletal muscle, Hand Strength, Kelch-Like ECH-Associated Protein 1 - biosynthesis, Kelch-Like ECH-Associated Protein 1 - genetics, Male, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Muscle Contraction - physiology, Muscle Fibers, Skeletal - metabolism, Muscle, Skeletal - metabolism, NF-E2-Related Factor 2 - deficiency, NF-E2-Related Factor 2 - genetics, NF-E2-Related Factor 2 - physiology, NQO1, Oxidation-Reduction, Physical Conditioning, Animal, Protein Transport, Quadriceps Muscle - metabolism, Running, Sequestosome-1 Protein - deficiency, Sequestosome-1 Protein - genetics, Sequestosome-1 Protein - physiology, Superoxide Dismutase - biosynthesis, Superoxide Dismutase - genetics, voluntary running