title: Antioxidant supplement inhibits skeletal muscle constitutive autophagy rather than fasting-induced autophagy in mice.
abstract: In this study, we tested the hypothesis that NAC administration leads to reduced oxidative stress and thus to decreased expression of autophagy markers in young mice. Our results reveal that NAC administration results in reduced muscle mRNA levels of several autophagy markers, including Beclin-1, Atg7, LC3, Atg9, and LAMP2. However, NAC supplement fails to block the activation of skeletal muscle autophagy in response to fasting, because fasting significantly increases the mRNA level of several autophagy markers and LC3 lipidation. We further examined the effects of NAC administration on mitochondrial antioxidant capacity in fed and 24-hour fasted mice. Our results clearly show that NAC administration depresses the expression of manganese superoxide dismutase (MnSOD) and TP53-induced glycolysis and apoptosis regulator (TIGAR), both of which play a predominant antioxidant role in mitochondria by reducing ROS level. In addition, we found no beneficial effect of NAC supplement on muscle mass but it can protect from muscle loss in response to fasting. Collectively, our findings indicate that ROS is required for skeletal muscle constitutive autophagy, rather than starvation-induced autophagy, and that antioxidant NAC inhibits constitutive autophagy by the regulation of mitochondrial ROS production and antioxidant capacity.
authors.affiliation: Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, China ; College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
authors.forename: Zhengtang
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, China ; College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: He
authors.affiliation: Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, China ; College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Ji
authors.affiliation: Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, China ; College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
authors.forename: Shuzhe
authors.initials: S
authors.lastname: Ding
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D019587:Dietary Supplements; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005215:Fasting / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D011506:Proteins; D017382:Reactive Oxygen Species; D006003:Glycogen; D013482:Superoxide Dismutase; D010744:Phosphoric Monoester Hydrolases; C554952:TIGAR protein, mouse; D000111:Acetylcysteine