Dose-dependent effect of nocodazole on the cytoskeleton of endothelial cells

K. M. Smurova, A. A. Birukova, Alexander Dmitriyevich Verin, I. B. Alieva

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Endothelium lining the internal surface of blood vessels carries out the barrier function and regulates vascular membrane permeability and thus provides an exchange of nutrients and metabolites between blood circulating in vessels and tissue liquids. Disturbances of the barrier function of endothelium are related with cytoskeletal reorganization, activation of actomyosin contraction, and gap formation. Microtubules are the first effector part in the reaction chains leading to the barrier disorder. Increased vascular permeability caused by endothelial dysfunction is observed in many human diseases and, in particular, emerges as a by-effect of mitosis-blocking drugs used for treatment of oncological diseases. In this study, we attempted to find a concentration of a mitostatic agent that would affect microtubules without significant interference with the endothelial barrier function. The population of microtubules in endothelial cells is heterogeneous; in the cytoplasm, alongside with dynamic microtubules, there present post-translationally modified microtubules, less dynamic and less susceptible to external influences. The area occupied by such stable microtubules in endothelial cells is rather significant (about one third of the cell area), and we have assumed that this may be a base of the resistance of the endothelial microtubule system to factors inducing barrier dysfunction. This assumption was examined using nocodazole as an inducer of the barrier dysfunction in endothelial cells. The effect of nocodazole on endothelial cell cytoskeleton is dose-dependent. At micromolar concentrations nocodazole causes an incurable damage of the barrier function and irreversibly upsets vital functions of cells. Treatment with nocodazole in nanomolar concentrations also causes an increase of endothelial monolayer permeability. However, in the concentration range 100-200 nM this effect is reversible. Treatment with 100 nM nocodazole leads to a partial disruption of microtubules near the cell margin without significant influence on the quantity of acetylated microtubules and actin filaments. Increase of the concentration up to 200 nM leads to a notable destruction of dynamic (but not acetylated) microtubules and also to an increase of the actin filament quantity in the central area of the cell. We suggest that the destruction of peripheral microtubules triggers the reaction cascade leading to the endothelial barrier dysfunction, but the presence of a significant amount of stable microtubules resistant to nanomolar concentrations of nocodazole helps to keep cell viability and also to restore functional activity.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalBiologicheskie Membrany
Volume25
Issue number3
StatePublished - Aug 13 2008

Fingerprint

Nocodazole
Endothelial cells
Cytoskeleton
Microtubules
Endothelial Cells
Actins
Actomyosin
Blood vessels
Capillary Permeability
Metabolites
Actin Cytoskeleton
Linings
Nutrients
Endothelium
Monolayers
Blood
Chemical activation
Cells
Tissue
Membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Smurova, K. M., Birukova, A. A., Verin, A. D., & Alieva, I. B. (2008). Dose-dependent effect of nocodazole on the cytoskeleton of endothelial cells. Biologicheskie Membrany, 25(3), 181-190.

Dose-dependent effect of nocodazole on the cytoskeleton of endothelial cells. / Smurova, K. M.; Birukova, A. A.; Verin, Alexander Dmitriyevich; Alieva, I. B.

In: Biologicheskie Membrany, Vol. 25, No. 3, 13.08.2008, p. 181-190.

Research output: Contribution to journalArticle

Smurova, KM, Birukova, AA, Verin, AD & Alieva, IB 2008, 'Dose-dependent effect of nocodazole on the cytoskeleton of endothelial cells', Biologicheskie Membrany, vol. 25, no. 3, pp. 181-190.
Smurova, K. M. ; Birukova, A. A. ; Verin, Alexander Dmitriyevich ; Alieva, I. B. / Dose-dependent effect of nocodazole on the cytoskeleton of endothelial cells. In: Biologicheskie Membrany. 2008 ; Vol. 25, No. 3. pp. 181-190.
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