Loss of skeletal muscle in cancer: biochemical mechanisms.

Michael J. Tisdale

Research output: Contribution to journalArticle

Abstract

Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.
Original languageEnglish
Pages (from-to)D164-D174
JournalFrontiers in Bioscience
Volume6
Publication statusPublished - 1 Feb 2001

Fingerprint

Muscle Neoplasms
Cachexia
Proteolysis
Muscle
Muscle Proteins
Skeletal Muscle
Tumors
Eicosapentaenoic Acid
Proteasome Endopeptidase Complex
Ubiquitin
Neoplasms
Appetite Stimulants
Chemical activation
Cathepsins
Degradation
Proteins
Respiratory Muscles
Oxidative stress
Pancreatic Neoplasms
Erosion

Keywords

  • skeletal muscle
  • cancer cachexia
  • protein degradation
  • ATP-ubiquitin-dependent proteolysis
  • tumour necrosis factor alpha
  • interleukin-6
  • interleukin-1
  • ciliary neurotrophic factor
  • interferon-gamma
  • proteolysis-inducing-factor
  • eicosapentaenoic acid
  • review

Cite this

Tisdale, Michael J. / Loss of skeletal muscle in cancer : biochemical mechanisms. In: Frontiers in Bioscience. 2001 ; Vol. 6. pp. D164-D174.
@article{4e8ca35c25714337b3ea30595fb5068d,
title = "Loss of skeletal muscle in cancer: biochemical mechanisms.",
abstract = "Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.",
keywords = "skeletal muscle, cancer cachexia, protein degradation, ATP-ubiquitin-dependent proteolysis, tumour necrosis factor alpha, interleukin-6, interleukin-1, ciliary neurotrophic factor, interferon-gamma, proteolysis-inducing-factor, eicosapentaenoic acid, review",
author = "Tisdale, {Michael J.}",
year = "2001",
month = "2",
day = "1",
language = "English",
volume = "6",
pages = "D164--D174",
journal = "Frontiers in Bioscience",
issn = "1093-9946",
publisher = "Frontiers in Bioscience",

}

Loss of skeletal muscle in cancer : biochemical mechanisms. / Tisdale, Michael J.

In: Frontiers in Bioscience, Vol. 6, 01.02.2001, p. D164-D174.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Loss of skeletal muscle in cancer

T2 - biochemical mechanisms.

AU - Tisdale, Michael J.

PY - 2001/2/1

Y1 - 2001/2/1

N2 - Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.

AB - Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.

KW - skeletal muscle

KW - cancer cachexia

KW - protein degradation

KW - ATP-ubiquitin-dependent proteolysis

KW - tumour necrosis factor alpha

KW - interleukin-6

KW - interleukin-1

KW - ciliary neurotrophic factor

KW - interferon-gamma

KW - proteolysis-inducing-factor

KW - eicosapentaenoic acid

KW - review

UR - http://www.scopus.com/inward/record.url?scp=0035259388&partnerID=8YFLogxK

UR - http://www.bioscience.org/2001/v6/d/tisdale/list.htm

M3 - Article

C2 - 11171557

VL - 6

SP - D164-D174

JO - Frontiers in Bioscience

JF - Frontiers in Bioscience

SN - 1093-9946

ER -