The Effects of Hypochlorous Acid on Skeletal Muscle Function: Implications for the Pathophysiology of Duchenne Muscular Dystrophy

Thomas Lea

doi:10.26182/4n3v-2c57

The Effects of Hypochlorous Acid on Skeletal Muscle Function: Implications for the Pathophysiology of Duchenne Muscular Dystrophy

Thomas Lea

Research output: Thesis › Doctoral Thesis

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Abstract

This thesis investigated the effects of hypochlorous acid (HOCl) on skeletal muscle function and implications for the pathophysiology of Duchenne Muscular Dystrophy (DMD). The mechanisms of muscle wasting in DMD remain unclear which is a significant barrier to developing treatments. The results from this thesis indicate that HOCl impairs muscle function via its effects on Ca2+ handling and contractile proteins and therefore may contribute to the pathophysiology of DMD. Increased levels of HOCl in dystrophic muscle may explain the link between inflammation, oxidative stress and impaired Ca2+ handling and represents an important target for the development of new DMD therapies.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Pinniger, Gavin, Supervisor Arthur, Peter, Supervisor Bakker, Tony, Supervisor
Thesis sponsors	Australian Government Research Training Program
Award date	19 Jan 2023
DOIs	https://doi.org/10.26182/4n3v-2c57
Publication status	Unpublished - 2023

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10.26182/4n3v-2c57

THESIS - DOCTOR OF PHILOSOPHY - LEA, Thomas Alexander - 2023
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1 Article

Effects of HOCl oxidation on excitation-contraction coupling: Implications for the pathophysiology of Duchenne muscular dystrophy
Lea, T. A., Pinniger, G. J., Arthur, P. G. & Bakker, T. J., 5 Sept 2022, In: The Journal of general physiology. 154, 9
Research output: Contribution to journal › Article › peer-review

Open Access
1 Citation (Web of Science)

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title = "The Effects of Hypochlorous Acid on Skeletal Muscle Function: Implications for the Pathophysiology of Duchenne Muscular Dystrophy",

abstract = "This thesis investigated the effects of hypochlorous acid (HOCl) on skeletal muscle function and implications for the pathophysiology of Duchenne Muscular Dystrophy (DMD). The mechanisms of muscle wasting in DMD remain unclear which is a significant barrier to developing treatments. The results from this thesis indicate that HOCl impairs muscle function via its effects on Ca2+ handling and contractile proteins and therefore may contribute to the pathophysiology of DMD. Increased levels of HOCl in dystrophic muscle may explain the link between inflammation, oxidative stress and impaired Ca2+ handling and represents an important target for the development of new DMD therapies.",

keywords = "Duchenne muscular dystrophy, Hypochlorous acid (HOCI), Skeletal muscle, Neuromuscular disease, Inflammation, Reactive Oxygen Species, Neutrophils, Myeloperoxidase",

author = "Thomas Lea",

year = "2023",

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language = "English",

school = "The University of Western Australia",

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N2 - This thesis investigated the effects of hypochlorous acid (HOCl) on skeletal muscle function and implications for the pathophysiology of Duchenne Muscular Dystrophy (DMD). The mechanisms of muscle wasting in DMD remain unclear which is a significant barrier to developing treatments. The results from this thesis indicate that HOCl impairs muscle function via its effects on Ca2+ handling and contractile proteins and therefore may contribute to the pathophysiology of DMD. Increased levels of HOCl in dystrophic muscle may explain the link between inflammation, oxidative stress and impaired Ca2+ handling and represents an important target for the development of new DMD therapies.

AB - This thesis investigated the effects of hypochlorous acid (HOCl) on skeletal muscle function and implications for the pathophysiology of Duchenne Muscular Dystrophy (DMD). The mechanisms of muscle wasting in DMD remain unclear which is a significant barrier to developing treatments. The results from this thesis indicate that HOCl impairs muscle function via its effects on Ca2+ handling and contractile proteins and therefore may contribute to the pathophysiology of DMD. Increased levels of HOCl in dystrophic muscle may explain the link between inflammation, oxidative stress and impaired Ca2+ handling and represents an important target for the development of new DMD therapies.

KW - Duchenne muscular dystrophy

KW - Hypochlorous acid (HOCI)

KW - Skeletal muscle

KW - Neuromuscular disease

KW - Inflammation

KW - Reactive Oxygen Species

KW - Neutrophils

KW - Myeloperoxidase

U2 - 10.26182/4n3v-2c57

DO - 10.26182/4n3v-2c57

M3 - Doctoral Thesis

ER -

The Effects of Hypochlorous Acid on Skeletal Muscle Function: Implications for the Pathophysiology of Duchenne Muscular Dystrophy

Abstract

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Research output

Effects of HOCl oxidation on excitation-contraction coupling: Implications for the pathophysiology of Duchenne muscular dystrophy

Cite this