Publication Date
2023
Document Type
Thesis
Committee Members
Hongmei Ren, Ph.D. (Advisor); Michael Markey, Ph.D. (Committee Member); Weiwen Long, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Duchenne muscular dystrophy (DMD) is a severe and progressive muscular dystrophy that develops in the skeletal muscles because of mutations in the dystrophin gene. Dystrophin stabilizes sarcolemma and assembles neuronal nitric oxide synthase (nNOS) into the dystrophin-associated protein complex on the sarcolemma. The absence of dystrophin triggers the delocalization of nNOS and contributes to the misregulation of muscle development, blood flow, muscle fatigue, and inflammation. Lipin1 was reduced in the skeletal muscles of patients with DMD and the mdx mouse model of DMD. In this study, we explored the role of lipin1 in the regulation of nNOS expression and function. We found that Lipin1 deficiency leads to the downregulation of nNOS protein and gene expression levels, while overexpression of lipin1 elevated nNOS protein and gene expression levels. We also found that Lipin1 upregulated nNOS gene expression by coactivating PPARα and binding to the promoter region of nNOS. Lipin1 deficiency leads to muscle fatigue in lipin1Myf5cKO mice, possibly due to the downregulation of nNOS. Most importantly, overexpressing lipin1 in dystrophic muscle improved muscle fatigue in our mdx:lipin1 transgenic mice which may be through the restoration of nNOS expression.
Page Count
74
Department or Program
Department of Biochemistry and Molecular Biology
Year Degree Awarded
2023
Copyright
Copyright 2023, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
