Activation of survival and apoptotic signaling pathways in lymphocytes exposed to palmitic acid.

Autor: Takahashi HK; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. hilton@icb.usp.br, Cambiaghi TD, Luchessi AD, Hirabara SM, Vinolo MA, Newsholme P, Curi R
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2012 Jan; Vol. 227 (1), pp. 339-50.
DOI: 10.1002/jcp.22740
Abstrakt: The toxicity of palmitic acid (PA) towards a human T-lymphocyte cell line (Jurkat) has been previously investigated but the mechanism(s) of PA action were unknown. In the current study, Jurkat cells were treated with sub-lethal concentrations of PA (50-150µM) and the activity of various signaling proteins was investigated. PA-induced apoptosis and mitochondrial dysfunction in a dose-dependent manner as evaluated by DNA fragmentation assay and depolarization of the mitochondrial membrane, respectively. PA treatment provoked release of cytochrome c from the inner mitochondrial membrane to the cytosol, activated members of the MAPK protein family JNK, p38, ERK, activated caspases 3/9, and increased oxidative/nitrosative stress. Exposure of cells to PA for 12 h increased insulin receptor (IR) and GLUT-4 levels in the plasma membrane. Insulin treatment (10 mU/ml/30 min) increased the phosphorylation of the IR β-subunit and Akt. A correlation was found between DNA fragmentation and expression levels of both IR and GLUT-4. Similar results were obtained for PA-treated lymphocytes from healthy human donors and from mesenteric lymph nodes of 48-h starved rats. PA stimulated glucose uptake by Jurkat cells (in the absence of insulin), stimulated accumulation of neutral lipids (triglyceride), and other lipid classes (phospholipids and cholesterol ester) but reduced glucose oxidation. Our results suggest that parameters of insulin signaling and non-oxidative glucose metabolism are stimulated as part of a coordinated response to prompt survival in lymphocytes exposed to PA but at higher concentrations, apoptosis prevails. These findings may explain aspects of lymphocyte dysfunction associated with diabetes.
(Copyright © 2011 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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