A long and winding road: defining the biological role and clinical importance of paraoxonases

Abstract

Paraoxonase-1 (

Functionality of HDL: Antioxidation and Detoxifying Effects

“…Early, in vitro studies suggested that purified PON1 and HDL-associated PON1 could protect LDL from oxidation (Mackness et al 2003), although these conclusions were questioned in subsequent reports (James 2006). However, studies from several animal models (James 2006) have provided much stronger support for the conclusion that PON1 protects against atherosclerotic disease by a process that involves reduction of oxidative stress.…”

“…However, studies from several animal models (James 2006) have provided much stronger support for the conclusion that PON1 protects against atherosclerotic disease by a process that involves reduction of oxidative stress. Thus PON1 knockout in mice was associated with a significant increase in the development of atherosclerotic lesions, whilst HDL from such mice were less able to protect LDL from oxidation (Shih et al 1998(Shih et al , 2000.…”

“…In a number of disease states that increase risk of atherosclerotic disease and where increased oxidative stress is noted, PON1 serum activity is significantly reduced. These include diabetes, the metabolic syndrome, familial hypercholesterolaemia and renal dysfunction (Abbott et al 1995;James 2006). Enzyme activity was also reduced in coronary disease patients, with the extent of coronary lesions correlating inversely with the PON1 activity (Graner et al 2006).…”

“…Indeed, HDL-associated PON1 has been shown to be a key determinant in detoxification of OPs (Shih et al 1998) in mouse models. Intriguingly, PON1 was shown to be associated with HDL at a time when its antioxidant activity was unknown (James 2006). A growing area of research is the importance of PON1 in environment toxicology and its role in susceptibility to OP exposure.…”

Development of an immunoblot assay with infrared fluorescence to quantify paraoxonase 1 in serum and plasma

“…Human paraoxonase 1 (PON1) is a calcium-dependent serum enzyme that is found in association with HDL (1). PON1 has a variety of substrates and has been found to have multiple polymorphisms in both the coding sequence (L55M, Q192R) and in the noncoding sequence (2).…”