Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 65, Issue -, Pages 978-987Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2013.08.163
Keywords
beta-cells; 4-hydroxyalkenals; Diabetes; Hormesis; Lipid peroxidation; Phospholipid remodeling; Vascular endothelial cells
Funding
- Israel Science Foundation [44/10]
- Brettler Center for Research of Molecular Pharmacology and Therapeutics in the Hebrew University
- COST (European Cooperation in Science and Technology) Action [CM1201]
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Peroxidation of polyunsaturated fatty acids is intensified in cells subjected to oxidative stress and results in the generation of various bioactive compounds, of which 4-hydroxyalkenals are prominent. During the progression of type 2 diabetes mellitus, the ensuing hyperglycemia promotes the generation of reactive oxygen species (ROS) that contribute to the development of diabetic complications. It has been suggested that ROS-induced lipid peroxidation and the resulting 4-hydroxyalkenals markedly contribute to the development and progression of these pathologies. Recent findings, however, also suggest that noncytotoxic levels of 4-hydroxyalkenals play important signaling functions in the early phase of diabetes and act as hormetic factors to induce adaptive and protective responses in cells, enabling them to function in the hyperglycemic milieu. Our studies and others' have proposed such regulatory functions for 4-hydroxynonenal and 4-hydroxydodecadienal in insulin secreting beta-cells and vascular endothelial cells, respectively. This review presents and discusses the mechanisms regulating the generation of 4-hydroxyalkenals under high glucose conditions and the molecular interactions underlying the reciprocal transition from hormetic to cytotoxic agents. (C) 2013 Elsevier Inc. All rights reserved.
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