Skeletal muscle‐specific DJ‐1 ablation‐induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy

作者：Shuang Zhang, Hongmei Yan, Jiyang Ding, Ruwen Wang, Ruwen Wang, Yonghao Feng, Xinyi Zhang, Xingyu Kong, Xingyu Kong, Hongyu Gong, Xiaodan Lü, Alice Ma, Yinghui Hua, Huan Liu, Jiani Guo, Huanqing Gao, Zhenqi Zhou, Ru Wang, Ru Wang, Peijie Chen, Tiemin Liu, Xingxing Kong, Xingxing Kong · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2023 · DOI：10.1002/jcsm.13290 · 被引用次数：21 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Neurological disorders and treatments、Parkinson's Disease and Spinal Disorders

BACKGROUND: DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored. METHODS: Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 del...