Modification of Delipidated Apoprotein B of Low Density Lipoprotein by Lipid Oxidation Products in Relation to Macrophage Scavenger Receptor Binding.

Abstract

It is known that macrophages recognize and take up oxidized low density lipoprotein (LDL) and this macrophage recognition has been suggested to be due to modification of the lysine (Lys) residues of apoprotein B (apo B). In order to determine whether such modification is involved in recognition, delipidated apo B was modified with lipid peroxidation products and the macrophage recognition of the modified apo B was examined. When delipidated apo B was treated with linoleic acid 13-mono-hydroperoxide (LOOH) and trans-2-octenal (octenal), apo B became fluorescent and its Lys and histidine (His) residues were decreased. When delipidated apo B, partially methylated at the epsilon-amino groups of Lys residues, was treated with LOOH and octenal, fluorescence was not produced and the free Lys residues were not decreased. LOOH- and octenal-modified delipidated apo B were recognized by mouse peritoneal macrophages. The macrophage recognition of the modified apo B was prevented by maleyl bovine serum albumin, indicating that the scavenger receptor was involved in recognition. Neither methyl apo B nor methyl apo B, modified with LOOH or octenal, was recognized by macrophages. Neutralization of positively charged Lys residues of apo B by modification with LOOH and octenal may be requisite for recognition. Bovine serum albumin modified with LOOH and octenal prevented the recognition of the modified apo B, indicating that none of the intrinsic structure of apo B is required for recognition.

The glycocalyx—linking albuminuria with renal and cardiovascular disease

“…47,48 Moreover, in kidney disease and diabetes mellitus, hyperglycaemia related peroxides and aldehydes glycate and carbamoylate lysine residues in albumin, thereby making it an ideal ligand for scavenger receptors. 49 Podocytes and tubular epithe lial cells possess a range of scavenger receptors, includ ing platelet glycoprotein 4 (CD36), RAGE, and C-X-C motif chemo kine 16. 50,51 In kidney disease and diabetes, podocyte damage could, therefore, be a consequence of albuminuria rather than a cause.…”

Detoxifying effects of ultrafiltration fractions of Dendrobium aphyllum peptides on chemical and AAPH-induced oxidative stress

“…6 Under conditions of excess ROS or dysfunctions in intrinsic defenses, oxidative stress occurs, leading to protein malformation, DNA damage, membrane phospholipid peroxidation, low-density lipoprotein modication, and aging-related problems, among other issues. 7,8 Inherent cellular defense systems consist of enzymatic and non-enzymatic antioxidants that maintain the balance between ROS production and destruction. 6 Peptides acting as antioxidants can mediate oxidation, including serving as free radical scavengers to directly quench singlet oxygen, chelating metals, synergistic interactions with primary antioxidants, and serving as antioxidative secondary compounds produced by peptides that react with oxidized lipids.…”

Scavenger Receptors on Sinusoidal Liver Endothelial Cells Are Involved in the Uptake of Aldehyde-Modified Proteins

“…Since this original description, a broad array of ligands for several classes of scavenger receptors have been described previously (Terpstra et al, 2000). In general, organic acid anhydrides, peroxides, and aldehydes (Brown et al, 1980) result in the modification of positively charged lysine residues to alter the charge on proteins to make them ideal scavenger receptor ligands (Alaiz et al, 1994). Receptors specifically recognizing aldehyde modified proteins were first described using formaldehyde-modified albumin (f-Alb) (Brown et al, 1980;Horiuchi et al, 1986;Takata et al, 1988Takata et al, , 1989Steinbrecher et al, 1989).…”