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Discovery of Carboxyethylpyrroles (CEPs): Critical Insights into AMD, Autism, Cancer, and Wound Healing from Basic Research on the Chemistry of Oxidized Phospholipids

Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA.
Chemical Research in Toxicology (Impact Factor: 4.19). 08/2011; 24(11):1803-16. DOI: 10.1021/tx200206v
Source: PubMed

ABSTRACT Basic research, exploring the hypothesis that 2-(ω-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modification of protein lysyl ε-amino groups by γ-hydroxyalkenal phospholipids that are formed by oxidative cleavage of docosahexaenate-containing phospholipids. Chemical synthesis of CEP-modified proteins and the production of highly specific antibodies that recognize them preceded and facilitated their detection in vivo and enabled exploration of their biological occurrence and activities. This investigational approach, from the chemistry of biomolecules to disease phenotype, is proving to be remarkably productive.

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    • "CEP condenses with certain amino acid residues forming covalent oxidized lipid-protein adducts [10]. Elevated levels of CEP-adducts are found in several pathological states including cancer, autistic brain tissue, atherosclerotic plaques, sites undergoing wound healing, and in AMD patients’ retinas [10]–[15]. Using a mouse model of AMD that utilizes CEP-immunization, we previously reported that in addition to signs of retinal damage mimicking AMD pathology in humans, CEP-immunized mice develop retinal infiltrating macrophages [16], [17]. In characterizing these macrophages we distinguished their polarization to be M1, not M2. "
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