Biochemical properties of cholesterol aldehyde secosterol and its derivatives

Abstract

Elevated levels of cholesterol aldehyde, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A, also called 5,6-secosterol), and its aldolization product (secosterol-B) have been detected in human atherosclerotic plaques and tissues samples of brains affected by neurodegeneration, such as Alzheimer’s disease and Lewy body dementia suggesting that increased formation of these compounds may be associated with inflammation-related diseases. Secosterol-A and secosterol-B, and also further oxidized products seco-A-COOH and seco-B-COOH induce several pro-inflammatory activities in vitro. Accumulating evidences demonstrate that the covalent bindings of these secosterols to target proteins seem to be critical to trigger their pro-inflammatory activities. One of the molecular mechanisms of protein adduct formations is that aldehydic function of secosterol-A and secosterol-B is reactive and form Schiff bases with ε- or N-terminal amino groups of proteins. In other cases, it is recently suggested that Michael acceptor moiety formed by the dehydration of not only secosterol-A and secosterol-B but also seco-A-COOH may react with nucleophilic site on target proteins. In this review, I summarize and provide an overview of formation mechanism of secosterols in in vitro and in vivo, patho- or physiological concentrations in biological and clinical samples, and molecular mechanisms of pro-inflammatory activities of secosterols.

Methods on LDL particle isolation, characterization, and component fractionation for the development of novel specific oxidized LDL status markers for atherosclerotic disease risk assessment

“…Starting with the oxidative modifications of the LDL lipid components, clinically important are those of cholesterol (free or esterified) and particularly the following: (i) Those carrying keto-groups (-C=O; i.e., in 7-keto-chol, and secosterol-B and -A with 1 and 2 keto-groups, respectively), to be quantified by a method under development by our lab. (ii) Those having a hydroperoxy group (HOO-; i.e., 5α-HOO-chol, 5β-HOO-chol, 6α-HOO-chol, and 6β-HOO-chol) ( 85 ); there is also the 7-HOO-chol, which is converted to the 7-keto-chol ( 86 ). Oxidatively modified cholesterol can also exist in its ester form, and is expected to translocate to the surface of the LDL particle as being polar (shown with large red arrows).…”