Resveratrol Ameliorates Mitophagy Disturbance and Improves Cardiac Pathophysiology of Dystrophin-deficient mdx Mice. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Kuno, Atsushi; Hosoda, Ryusuke; Sebori, Rio; Hayashi, Takashi; Sakuragi, Hiromi; Tanabe, Mika; Horio, Yoshiyuki
• Is Part Of: Scientific reports. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 12
• Publication Date: 2018-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-018-33930-w
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Autophagy activation improves the phenotype inmdx mice, a Duchenne muscular dystrophy (DMD) model, although the underlying mechanisms are obscure. We previously found that resveratrol, a strong inducer of autophagy, ameliorates the cardiac pathology ofmdx mice. Autophagy could eliminate damaged mitochondria, a major source of intracellular reactive oxygen species (ROS), although there is no evidence for mitochondriopathy in dystrophic cardiomyopathy. To elucidate resveratrol's function, we investigated the deletion of mitochondrial DNA (mtDNA), autophagy of damaged mitochondria (mitophagy), and ROS accumulation in themdx mouse heart. Low levels of normal mtDNA and abnormal accumulations of mitochondria-containing autophagosomes were found in themdx mouse heart. Administering resveratrol tomdx mice for 56 weeks ameliorated the cardiomyopathy, with significant reductions in the amount of mtDNA deletion, the number of mitochondria-containing autophagosomes, and the ROS levels. Resveratrol induced nuclear FoxO3a accumulation and the expression of autophagy-related genes, which are targets of FoxOs. The most effective dose inmdx mice was 0.4 g resveratrol/kg food. In conclusion, resveratrol improved cardiomyopathy by promoting mitophagy in themdx mouse heart. We propose that acquired mitochondriopathy worsens the pathology of DMD and is a potential therapeutic target for the cardiomyopathy in DMD patients.