Exercise modulates redox-sensitive small GTPase activity in the brain microvasculature in a model of brain metastasis formation

Gretchen Wolff, Jordan E. Balke, Ibolya Edit Andras, Minseon Park, Michal J Toborek

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB). There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0±0.3 km/day. Mice were then infused with 1.0×106 D122 (murine Lewis lung carcinoma) cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies) or 2-3 weeks (in long-term studies) post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals.

Original languageEnglish
Article numbere97033
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 7 2014

Fingerprint

Monomeric GTP-Binding Proteins
guanosinetriphosphatase
Microvessels
metastasis
Oxidation-Reduction
Tumors
Brain
exercise
Neoplasm Metastasis
brain
Cells
mice
Running
Neoplasms
Chemical activation
cell invasion
Oxidative stress
blood-brain barrier
Lewis Lung Carcinoma
Cell growth

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Exercise modulates redox-sensitive small GTPase activity in the brain microvasculature in a model of brain metastasis formation. / Wolff, Gretchen; Balke, Jordan E.; Andras, Ibolya Edit; Park, Minseon; Toborek, Michal J.

In: PLoS One, Vol. 9, No. 5, e97033, 07.05.2014.

Research output: Contribution to journalArticle

@article{7201978ec46a4cd0af75de94ddd8fa89,
title = "Exercise modulates redox-sensitive small GTPase activity in the brain microvasculature in a model of brain metastasis formation",
abstract = "Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB). There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0±0.3 km/day. Mice were then infused with 1.0×106 D122 (murine Lewis lung carcinoma) cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies) or 2-3 weeks (in long-term studies) post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals.",
author = "Gretchen Wolff and Balke, {Jordan E.} and Andras, {Ibolya Edit} and Minseon Park and Toborek, {Michal J}",
year = "2014",
month = "5",
day = "7",
doi = "10.1371/journal.pone.0097033",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - Exercise modulates redox-sensitive small GTPase activity in the brain microvasculature in a model of brain metastasis formation

AU - Wolff, Gretchen

AU - Balke, Jordan E.

AU - Andras, Ibolya Edit

AU - Park, Minseon

AU - Toborek, Michal J

PY - 2014/5/7

Y1 - 2014/5/7

N2 - Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB). There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0±0.3 km/day. Mice were then infused with 1.0×106 D122 (murine Lewis lung carcinoma) cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies) or 2-3 weeks (in long-term studies) post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals.

AB - Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB). There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0±0.3 km/day. Mice were then infused with 1.0×106 D122 (murine Lewis lung carcinoma) cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies) or 2-3 weeks (in long-term studies) post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals.

UR - http://www.scopus.com/inward/record.url?scp=84900532831&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900532831&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0097033

DO - 10.1371/journal.pone.0097033

M3 - Article

C2 - 24804765

AN - SCOPUS:84900532831

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e97033

ER -