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Colon 26 adenocarcinoma (C26)-induced cancer cachexia impairs skeletal muscle mitochondrial function and content

  • Daria NeyroudEmail author
  • Rachel L. Nosacka
  • Andrew R. Judge
  • Russell T. Hepple
Rapid Communication
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Abstract

The present study aimed to determine the impact of colon 26 adenocarcinoma (C26)-induced cancer cachexia on skeletal muscle mitochondrial respiration and content. Twelve male CD2F1 mice were injected with C26-cells (tumor bearing (TB) group), whereas 12 age-matched mice received PBS vehicle injection (non-tumor bearing (N-TB) group). Mitochondrial respiration was studied in saponin-permeabilized soleus myofibers. TB mice showed lower body weight (~ 20%) as well as lower soleus, gastrocnemius-plantaris complex and tibialis anterior masses versus N-TB mice (p < 0.05). Soleus maximal state III mitochondrial respiration was 20% lower (10 mM glutamate, 5 mM malate, 5 mM adenosine diphosphate; p < 0.05) and acceptor control ratio (state III/state II) was 15% lower in the TB vs. N-TB (p < 0.05), with the latter suggesting uncoupling. Lower VDAC protein content suggested reduced mitochondrial content in TB versus N-TB (p < 0.05). Skeletal muscle in C26-induced cancer cachexia exhibits reductions in: maximal mitochondrial respiration capacity, mitochondrial coupling and mitochondrial content.

Keywords

Mitochondrial respiration Mitochondrial coupling Mitochondrial homeostasis Muscle wasting Mitochondrial content Oxidative phosphorylation 

Abbreviations

ACR

Acceptor control ratio

ADP

Adenosine diphosphate

BSA

Bovine serum albumin

C26

Colon 26 adenocarcinoma

DTT

Dithiotreitol

EGTA

Ethylene glycol-bis-(2-aminoethylether)-N, N, N’, N’-tetraacetic acid

G

Glutamate

GasPL

Gastrocnemii-plantaris complex

K-MES

2-(N-morpholino) ethanesulfonic acid potassium salt

LLC

Lewis lung carcinoma

M

Malate

N-TB

Non-tumor bearing

PBS

Phosphate buffer saline

TB

Tumor bearing

TBS-T

Tris-buffered saline containing 0.1% of Tween

Notes

Acknowledgements

This work was supported by funds provided by the University of Florida Cancer Center (to RTH) and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (R01AR060209 to ARJ). Daria Neyroud was supported by the Swiss National Science Foundation (P2GEP3_168384). The authors greatly thank Yana Konokhova for her help during tissue harvest.

Compliance with ethical standards

Conflict of interest

All authors declared that they have no competing interests.

Ethical approval

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Physical TherapyUniversity of FloridaGainesvilleUSA

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