Weight gain does not preclude increased ubiquitin conjugation in skeletal muscle

An exploratory study in tumor-bearing mice

Aminah Jatoi, Margot P. Cleary, Cheow Meng Tee, Phuong L. Nguyen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and Hypothesis: At least 13 studies have shown that the ubiquitin-proteasome system mediates muscle wasting in weight-losing cancer subjects. We hypothesized that cancer itself may activate the ubiquitin-proteasome system, regardless of weight loss. Methods: We utilized hybrid mice obtained by crossing Mouse Mammary Tumor Virus-Transforming Growth Factor-α (TGF-α) mice with the Lepob strain. Five hybrid MMTV-TGF-α heterozygous Lep+Lepob female mice with mammary tumors were used; 4 nontransgenic heterozygous Lep+Lepob female mice served as controls. Ubiquitin conjugates were quantitated from hamstring and paraspinal muscles by Western blotting. Myocyte apoptosis was determined by a modified TUNEL assay. Results: All mice gained weight, even after tumor development. Higher concentrations of muscle ubiquitin conjugates were seen in the 5 tumor-bearing, TGF-α transgenic mice as compared with the 4 non-tumor-bearing mice: median (range) in arbitrary densitometric units: 0.67 (0.22-4.59) versus 0.18 (0.08-0.44) in hamstring muscle and 0.56 (0.23-20.15) versus 0.18 (0.08-0.25) in paraspinal muscle (p = 0.04 and p = 0.04, respectively; Mann-Whitney U test). Apoptosis was not seen in any muscle sample studied. Conclusions: Ubiquitin conjugates are increased in the skeletal muscle of tumor-bearing mice in the absence of weight loss. Such activation is not seen in the skeletal muscle on non-tumor-bearing mice. Further studies might focus of whether this observation is relevant to cancer-associated wasting of lean tissue.

Original languageEnglish (US)
Pages (from-to)116-120
Number of pages5
JournalAnnals of Nutrition and Metabolism
Volume45
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Ubiquitin
Weight Gain
Skeletal Muscle
Neoplasms
Transforming Growth Factors
Paraspinal Muscles
Proteasome Endopeptidase Complex
Muscles
Weight Loss
Apoptosis
Mouse mammary tumor virus
Weights and Measures
In Situ Nick-End Labeling
Nonparametric Statistics
Muscle Cells
Transgenic Mice
Western Blotting
Breast Neoplasms

Keywords

  • Cachexia
  • Cancer
  • Muscle
  • Ubiquitin
  • Wasting

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Weight gain does not preclude increased ubiquitin conjugation in skeletal muscle : An exploratory study in tumor-bearing mice. / Jatoi, Aminah; Cleary, Margot P.; Tee, Cheow Meng; Nguyen, Phuong L.

In: Annals of Nutrition and Metabolism, Vol. 45, No. 3, 2001, p. 116-120.

Research output: Contribution to journalArticle

@article{008f9749628447358240587af6481344,
title = "Weight gain does not preclude increased ubiquitin conjugation in skeletal muscle: An exploratory study in tumor-bearing mice",
abstract = "Background and Hypothesis: At least 13 studies have shown that the ubiquitin-proteasome system mediates muscle wasting in weight-losing cancer subjects. We hypothesized that cancer itself may activate the ubiquitin-proteasome system, regardless of weight loss. Methods: We utilized hybrid mice obtained by crossing Mouse Mammary Tumor Virus-Transforming Growth Factor-α (TGF-α) mice with the Lepob strain. Five hybrid MMTV-TGF-α heterozygous Lep+Lepob female mice with mammary tumors were used; 4 nontransgenic heterozygous Lep+Lepob female mice served as controls. Ubiquitin conjugates were quantitated from hamstring and paraspinal muscles by Western blotting. Myocyte apoptosis was determined by a modified TUNEL assay. Results: All mice gained weight, even after tumor development. Higher concentrations of muscle ubiquitin conjugates were seen in the 5 tumor-bearing, TGF-α transgenic mice as compared with the 4 non-tumor-bearing mice: median (range) in arbitrary densitometric units: 0.67 (0.22-4.59) versus 0.18 (0.08-0.44) in hamstring muscle and 0.56 (0.23-20.15) versus 0.18 (0.08-0.25) in paraspinal muscle (p = 0.04 and p = 0.04, respectively; Mann-Whitney U test). Apoptosis was not seen in any muscle sample studied. Conclusions: Ubiquitin conjugates are increased in the skeletal muscle of tumor-bearing mice in the absence of weight loss. Such activation is not seen in the skeletal muscle on non-tumor-bearing mice. Further studies might focus of whether this observation is relevant to cancer-associated wasting of lean tissue.",
keywords = "Cachexia, Cancer, Muscle, Ubiquitin, Wasting",
author = "Aminah Jatoi and Cleary, {Margot P.} and Tee, {Cheow Meng} and Nguyen, {Phuong L.}",
year = "2001",
doi = "10.1159/000046716",
language = "English (US)",
volume = "45",
pages = "116--120",
journal = "Annals of Nutrition and Metabolism",
issn = "0250-6807",
publisher = "S. Karger AG",
number = "3",

}

TY - JOUR

T1 - Weight gain does not preclude increased ubiquitin conjugation in skeletal muscle

T2 - An exploratory study in tumor-bearing mice

AU - Jatoi, Aminah

AU - Cleary, Margot P.

AU - Tee, Cheow Meng

AU - Nguyen, Phuong L.

PY - 2001

Y1 - 2001

N2 - Background and Hypothesis: At least 13 studies have shown that the ubiquitin-proteasome system mediates muscle wasting in weight-losing cancer subjects. We hypothesized that cancer itself may activate the ubiquitin-proteasome system, regardless of weight loss. Methods: We utilized hybrid mice obtained by crossing Mouse Mammary Tumor Virus-Transforming Growth Factor-α (TGF-α) mice with the Lepob strain. Five hybrid MMTV-TGF-α heterozygous Lep+Lepob female mice with mammary tumors were used; 4 nontransgenic heterozygous Lep+Lepob female mice served as controls. Ubiquitin conjugates were quantitated from hamstring and paraspinal muscles by Western blotting. Myocyte apoptosis was determined by a modified TUNEL assay. Results: All mice gained weight, even after tumor development. Higher concentrations of muscle ubiquitin conjugates were seen in the 5 tumor-bearing, TGF-α transgenic mice as compared with the 4 non-tumor-bearing mice: median (range) in arbitrary densitometric units: 0.67 (0.22-4.59) versus 0.18 (0.08-0.44) in hamstring muscle and 0.56 (0.23-20.15) versus 0.18 (0.08-0.25) in paraspinal muscle (p = 0.04 and p = 0.04, respectively; Mann-Whitney U test). Apoptosis was not seen in any muscle sample studied. Conclusions: Ubiquitin conjugates are increased in the skeletal muscle of tumor-bearing mice in the absence of weight loss. Such activation is not seen in the skeletal muscle on non-tumor-bearing mice. Further studies might focus of whether this observation is relevant to cancer-associated wasting of lean tissue.

AB - Background and Hypothesis: At least 13 studies have shown that the ubiquitin-proteasome system mediates muscle wasting in weight-losing cancer subjects. We hypothesized that cancer itself may activate the ubiquitin-proteasome system, regardless of weight loss. Methods: We utilized hybrid mice obtained by crossing Mouse Mammary Tumor Virus-Transforming Growth Factor-α (TGF-α) mice with the Lepob strain. Five hybrid MMTV-TGF-α heterozygous Lep+Lepob female mice with mammary tumors were used; 4 nontransgenic heterozygous Lep+Lepob female mice served as controls. Ubiquitin conjugates were quantitated from hamstring and paraspinal muscles by Western blotting. Myocyte apoptosis was determined by a modified TUNEL assay. Results: All mice gained weight, even after tumor development. Higher concentrations of muscle ubiquitin conjugates were seen in the 5 tumor-bearing, TGF-α transgenic mice as compared with the 4 non-tumor-bearing mice: median (range) in arbitrary densitometric units: 0.67 (0.22-4.59) versus 0.18 (0.08-0.44) in hamstring muscle and 0.56 (0.23-20.15) versus 0.18 (0.08-0.25) in paraspinal muscle (p = 0.04 and p = 0.04, respectively; Mann-Whitney U test). Apoptosis was not seen in any muscle sample studied. Conclusions: Ubiquitin conjugates are increased in the skeletal muscle of tumor-bearing mice in the absence of weight loss. Such activation is not seen in the skeletal muscle on non-tumor-bearing mice. Further studies might focus of whether this observation is relevant to cancer-associated wasting of lean tissue.

KW - Cachexia

KW - Cancer

KW - Muscle

KW - Ubiquitin

KW - Wasting

UR - http://www.scopus.com/inward/record.url?scp=0034937750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034937750&partnerID=8YFLogxK

U2 - 10.1159/000046716

DO - 10.1159/000046716

M3 - Article

VL - 45

SP - 116

EP - 120

JO - Annals of Nutrition and Metabolism

JF - Annals of Nutrition and Metabolism

SN - 0250-6807

IS - 3

ER -