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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Aflaki, E; Balenga, NA; Luschnig-Schratl, P; Wolinski, H; Povoden, S; Chandak, PG; Bogner-Strauss, JG; Eder, S; Konya, V; Kohlwein, SD; Heinemann, A; Kratky, D.
Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis.
Cell Mol Life Sci. 2011; 68(23): 3933-3947. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG Google Scholar


Autor/innen der Med Uni Graz:
Aflaki Elma
Chandak Prakash Gopal Das
Heinemann Akos
Konya Viktoria
Kratky Dagmar
Luschnig Petra

Dimensions Citations:

Plum Analytics:
Number of Figures: 7
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Infiltration of monocytes and macrophages into the site of inflammation is critical in the progression of inflammatory diseases such as atherosclerosis. Cell migration is dependent on the continuous organization of the actin cytoskeleton, which is regulated by members of the small Rho GTPase family (RhoA, Cdc42, Rac) that are also important for the regulation of signal transduction pathways. We have recently reported on reduced plaque formation in an atherosclerotic mouse model transplanted with bone marrow from adipose triglyceride lipase-deficient (Atgl-/-) mice. Here we provide evidence that defective lipolysis in macrophages lacking ATGL, the major enzyme responsible for triacylglycerol hydrolysis, favors an anti-inflammatory M2-like macrophage phenotype. Our data implicate an as yet unrecognized principle that insufficient lipolysis influences macrophage polarization and actin polymerization, resulting in impaired macrophage migration. Sustained phosphorylation of focal adhesion kinase [due to inactivation of its phosphatase by elevated levels of reactive oxygen species (ROS)] results in defective Cdc42, Rac1 and RhoA activation and in increased and sustained activation of Rac2. Inhibition of ROS production restores the migratory capacity of Atgl-/- macrophages. Since monocyte and macrophage migration are a prerequisite for infiltrating the arterial wall, our results provide a molecular link between lipolysis and the development of atherosclerosis.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Movement -
Cell Polarity -
Female -
Lipase - deficiency
Lipolysis -
Macrophages - enzymology
Male -
Mice -
Mice, Inbred C57BL -
Mice, Knockout -
Reactive Oxygen Species - antagonists and inhibitors
rho GTP-Binding Proteins - metabolism

Find related publications in this database (Keywords)
Small Rho GTPases
Adipose triglyceride lipase
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