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Satellite Stem Cells and Muscular Dystrophy01:21

Satellite Stem Cells and Muscular Dystrophy

Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
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Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
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There are three types of cytoskeletal structures in eukaryotic cells—microfilaments, intermediate filaments, and microtubules. With a diameter of about 25 nm, microtubules are the thickest of these fibers. Microtubules carry out a variety of functions that include cell structure and support, transport of organelles, cell motility (movement), and the separation of chromosomes during cell division.
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Microtubules underlie dysfunction in duchenne muscular dystrophy.

Ramzi J Khairallah1, Guoli Shi, Francesca Sbrana

  • 1Center for Biomedical Engineering and Technology and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Science Signaling
|August 9, 2012
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Summary

Microtubules drive calcium and reactive oxygen species (ROS) signaling dysfunction in Duchenne muscular dystrophy (DMD). Disrupting microtubules or NADPH oxidase 2 reduces muscle injury in DMD mouse models.

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Isometric and Eccentric Force Generation Assessment of Skeletal Muscles Isolated from Murine Models of Muscular Dystrophies

Published on: January 31, 2013

Area of Science:

  • Cell Biology
  • Biochemistry
  • Genetics

Background:

  • Duchenne muscular dystrophy (DMD) is a fatal X-linked myopathy.
  • Absence of dystrophin in DMD leads to microtubule cytoskeleton disorganization.
  • Mechanotransduction signaling, involving calcium (Ca2+) and reactive oxygen species (ROS), contributes to muscle degeneration in DMD.

Purpose of the Study:

  • To investigate the role of microtubules in aberrant Ca2+ and ROS signaling in DMD.
  • To identify microtubules as potential therapeutic targets for DMD.

Main Methods:

  • Studied adult mdx mice (a DMD model) and wild-type mice.
  • Utilized physiologic stretch to elicit responses in muscle cells.
  • Examined microtubule disruption using colchicine and nocodazole.
  • Analyzed NADPH oxidase activity and ROS production (X-ROS).
  • Performed transcriptome analysis on human DMD skeletal muscle.

Main Results:

  • Physiologic stretch induced microtubule-dependent X-ROS production in mdx mouse muscle.
  • X-ROS amplified Ca2+ influx via stretch-activated channels in mdx muscle.
  • Dense microtubule networks correlated with increased X-ROS and Ca2+ influx.
  • Disrupting microtubules or inhibiting NADPH oxidase 2 reduced muscle injury in vivo.
  • Human DMD muscle showed increased expression of X-ROS-related genes.

Conclusions:

  • Microtubules are the primary drivers of Ca2+ and ROS signaling dysfunction in DMD.
  • Targeting microtubules represents a promising therapeutic strategy for DMD.