This Article Full Text Full Text (PDF) All Versions of this Article: 148/4/1622    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chai, W. Articles by Liu, Z. Search for Related Content PubMed PubMed Citation Articles by Chai, W. Articles by Liu, Z.

p38 Mitogen-Activated Protein Kinase Mediates Palmitate-Induced Apoptosis But Not Inhibitor of Nuclear Factor-B Degradation in Human Coronary Artery Endothelial Cells

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22908-1410

Address all correspondence and requests for reprints to: Zhenqi Liu, M.D., Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, P.O. Box 801410, Charlottesville, Virginia 22908-1410. E-mail: zl3e{at}virginia.edu.

Plasma free fatty acids are elevated in patients with type 2 diabetes and contribute to the pathogenesis of insulin resistance and endothelial dysfunction. The p38 MAPK mediates stress, inflammation, and apoptosis. Whether free fatty acids induce apoptosis and/or activate nuclear factor-B inflammatory pathway in human coronary artery endothelial cells (hCAECs) and, if so, whether this involves the p38 MAPK pathway is unknown. hCAECs (passages 4–6) were grown to 70% confluence and then incubated with palmitate at concentrations of 0–300 µM for 6–48 h. Palmitate at 100, 200, or 300 µM markedly increased apoptosis after 12 h of incubation. This apoptotic effect was time (P = 0.008) and dose (P = 0.006) dependent. Palmitate (100 µM for 24 h) induced a greater than 2-fold increase in apoptosis, which was accompanied with a 4-fold increase in p38 MAPK activity (P < 0.001). Palmitate did not affect the phosphorylation of Akt1 or ERK1/2. SB203580 (a specific inhibitor of p38 MAPK) alone did not affect cellular apoptosis; however, it abolished palmitate-induced apoptosis and p38 MAPK activation. Palmitate significantly reduced the level of inhibitor of nuclear factor-B (IB). However, treatment of cells with SB203580 did not restore IB to baseline. We conclude that palmitate induces hCAEC apoptosis via a p38 MAPK-dependent mechanism and may participate in coronary endothelial injury in diabetes. However, palmitate-mediated IB degradation in hCAECs is independent of p38 MAPK activity.

This article has been cited by other articles:

				W. Chai, Y. Wu, G. Li, W. Cao, Z. Yang, and Z. Liu Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E183 - E189. [Abstract] [Full Text] [PDF]

				G. Li, E. J. Barrett, M. O. Barrett, W. Cao, and Z. Liu Tumor Necrosis Factor-{alpha} Induces Insulin Resistance in Endothelial Cells via a p38 Mitogen-Activated Protein Kinase-Dependent Pathway Endocrinology, July 1, 2007; 148(7): 3356 - 3363. [Abstract] [Full Text] [PDF]