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Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
ERK1/2 regulates two sequential steps promoting monocyte survival to peroxynitrite
1Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino "Carlo Bo", Via Santa Chiara, Urbino (PU), Italy.
Journal of Cellular Physiology
|September 26, 2006
Summary
Extracellular regulated kinase 1/2 (ERK1/2) controls 5-lipoxygenase (5-LO) activation, crucial for preventing peroxynitrite-induced cell death. This pathway is vital for monocyte/macrophage survival.
Area of Science:
- Cellular Biology
- Biochemistry
- Immunology
Background:
- Cytosolic phospholipase A2 (cPLA2)-derived arachidonic acid promotes monocyte/macrophage survival against peroxynitrite.
- This involves 5-lipoxygenase (5-LO) metabolism to 5-hydroxyeicosatetraenoic acid and protein kinase Calpha (PKCalpha) mitochondrial translocation.
- This process is linked to Bad and Bax cytosolic accumulation.
Purpose of the Study:
- To investigate the role of extracellular regulated kinase 1/2 (ERK1/2) in regulating 5-LO activation and monocyte/macrophage survival.
- To elucidate the signaling pathway downstream of ERK1/2 in response to peroxynitrite toxicity.
Main Methods:
- Inhibition of ERK1/2 signaling pathway.
- Analysis of protein localization (PKCalpha, Bad, Bax) using cell fractionation.
- Assessment of cell death via mitochondrial permeability transition.
Main Results:
- ERK1/2 inhibition led to cytosolic PKCalpha and mitochondrial Bad/Bax accumulation.
- ERK1/2 inhibition resulted in rapid necrosis mediated by mitochondrial permeability transition.
- Nanomolar 5-hydroxyeicosatetraenoic acid prevented these detrimental effects.
Conclusions:
- ERK1/2 critically regulates 5-LO activation and nuclear translocation.
- ERK1/2 is essential for survival signaling that prevents peroxynitrite-induced toxicity.
- ERK1/2's role extends beyond cPLA2, directly impacting 5-LO activity.
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