Glycoxydation promotes vascular damage Via MAPK-ERK/JNK pathways

Filomena de Nigris, Monica Rienzo, Marcella Sessa, Teresa Infante, Elena Cesario, Louis J. Ignarro, Mohammed Al-Omran, Antonio Giordano, Wulf Palinski, Claudio Napoli

Research output: Contribution to journalArticle

Abstract

Oxidation and glycation enhance foam cell formation via MAPK/JNK in euglycemic and diabetic subjects. Here, we investigated the effects of glycated and oxidized LDL (glc-oxLDL) on MAPK-ERK and JNK signaling pathways using human coronary smooth muscle cells. Glc-oxLDL induced a broad cascade of MAPK/JNK-dependent signaling transduction pathways and the AP-1 complex. In glc-oxLDL treated coronary arterioles, tumor necrosis factor (TNF) α increased JNK phosphorylation, whereas protein kinase inhibitor dimethylaminopurine (DMAP) prevented the TNF-induced increase in JNK phosphorylation. The role of MKK4 and JNK were then investigated in vivo, using apolipoprotein E knockout (ApoE-/-) mice. Peritoneal macrophages, isolated from spontaneously hyperlipidemic but euglycemic mice showed increases in both proteins and phosphorylated proteins. Compared to streptozotocin-treated diabetic C57BL6 and nondiabetic C57BL6 Wt mice, in streptozotocin-diabetic ApoE-/- mice, the increment of foam cell formation corresponded to an increment of phosphorylation of JNK1, JNK2, and MMK4. Thus, we provide a first line of evidence that MAPK-ERK/JNK pathways are involved in vascular damage induced by glycoxidation.

Original languageEnglish
Pages (from-to)3639-3647
Number of pages9
JournalJournal of Cellular Physiology
Volume227
Issue number11
DOIs
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    de Nigris, F., Rienzo, M., Sessa, M., Infante, T., Cesario, E., Ignarro, L. J., Al-Omran, M., Giordano, A., Palinski, W., & Napoli, C. (2012). Glycoxydation promotes vascular damage Via MAPK-ERK/JNK pathways. Journal of Cellular Physiology, 227(11), 3639-3647. https://doi.org/10.1002/jcp.24070