Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice

Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disease manifesting itself with tremors, muscle stiffness, bradykinesia, dementia, and depression. Mutations of mitochondrial E3 ligase, PARKIN, have been associated with juvenile PD. Previous studies have characterized mus...

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Main Authors: Peker, Nesibe, Sharma, Mridula, Kambadur, Ravi
Other Authors: School of Biological Sciences
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Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/164654
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spelling sg-ntu-dr.10356-1646542023-02-28T17:13:58Z Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice Peker, Nesibe Sharma, Mridula Kambadur, Ravi School of Biological Sciences Singapore Institute for Clinical Sciences Science::Biological sciences Metabolic Homeostasis Ubiquitin Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disease manifesting itself with tremors, muscle stiffness, bradykinesia, dementia, and depression. Mutations of mitochondrial E3 ligase, PARKIN, have been associated with juvenile PD. Previous studies have characterized muscle atrophy and motor deficits upon loss of functional Parkin in fly and rodent models. However, the mechanisms behind pathophysiology of Parkin deficient muscle remains to be elusive. Here, results suggested that knock down of Parkin significantly increases proteolytic activities in skeletal muscle cell line, the C2C12 myotubes. However, the atrogene levels increase moderately in Parkin deficient cell line. To further investigate the role of Parkin in skeletal muscle atrophy, Parkin knock out (KO) and wild type mice were subjected to 48 h starvation. After 48 h fasting, a greater reduction in skeletal muscle weights was observed in Parkin KO mice as compared to age matched wild type control, suggesting elevated proteolytic activity in the absence of Parkin. Subsequent microarray analyses revealed further enhanced expression of FOXO and ubiquitin pathway in fasted Parkin KO mice. Furthermore, a greater reduction in the expression of cytoskeleton genes was observed in Parkin KO mice following 48 h fasting. Collectively, these results suggest that Parkin deficiency exacerbates fasting-induced skeletal muscle wasting, through upregulating genes involved in catabolic activities in skeletal muscle. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University Published version This work was supported by Nanyang Technological University, National University of Singapore, and Singapore Institute for Clinical Sciences. N.P. was supported with PhD and Postdoctoral fellowships by TEV-SINGA, A*STAR and Nanyang Technological University. 2023-02-07T07:49:33Z 2023-02-07T07:49:33Z 2022 Journal Article Peker, N., Sharma, M. & Kambadur, R. (2022). Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice. NPJ Parkinson's Disease, 8(1). https://dx.doi.org/10.1038/s41531-022-00419-3 2373-8057 https://hdl.handle.net/10356/164654 10.1038/s41531-022-00419-3 36396647 2-s2.0-85142214968 1 8 en NPJ Parkinson's Disease © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Metabolic Homeostasis
Ubiquitin
spellingShingle Science::Biological sciences
Metabolic Homeostasis
Ubiquitin
Peker, Nesibe
Sharma, Mridula
Kambadur, Ravi
Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice
description Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disease manifesting itself with tremors, muscle stiffness, bradykinesia, dementia, and depression. Mutations of mitochondrial E3 ligase, PARKIN, have been associated with juvenile PD. Previous studies have characterized muscle atrophy and motor deficits upon loss of functional Parkin in fly and rodent models. However, the mechanisms behind pathophysiology of Parkin deficient muscle remains to be elusive. Here, results suggested that knock down of Parkin significantly increases proteolytic activities in skeletal muscle cell line, the C2C12 myotubes. However, the atrogene levels increase moderately in Parkin deficient cell line. To further investigate the role of Parkin in skeletal muscle atrophy, Parkin knock out (KO) and wild type mice were subjected to 48 h starvation. After 48 h fasting, a greater reduction in skeletal muscle weights was observed in Parkin KO mice as compared to age matched wild type control, suggesting elevated proteolytic activity in the absence of Parkin. Subsequent microarray analyses revealed further enhanced expression of FOXO and ubiquitin pathway in fasted Parkin KO mice. Furthermore, a greater reduction in the expression of cytoskeleton genes was observed in Parkin KO mice following 48 h fasting. Collectively, these results suggest that Parkin deficiency exacerbates fasting-induced skeletal muscle wasting, through upregulating genes involved in catabolic activities in skeletal muscle.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Peker, Nesibe
Sharma, Mridula
Kambadur, Ravi
format Article
author Peker, Nesibe
Sharma, Mridula
Kambadur, Ravi
author_sort Peker, Nesibe
title Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice
title_short Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice
title_full Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice
title_fullStr Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice
title_full_unstemmed Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice
title_sort parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice
publishDate 2023
url https://hdl.handle.net/10356/164654
_version_ 1759855838474797056