Increased methionine sulfoxide content of apoA-I in type 1 diabetes

Brock, Jonathan W. C.; Jenkins, Alicia J.; Lyons, Timothy J.; Klein, Richard L.; Yim, Eunsil; Lopes‐Virella, Maria F.; Carter, Rickey E.; Dcct,; Thorpe, Suzanne R.; Baynes, John W.

doi:10.1194/jlr.m800015-jlr200

Cited by 44 publications

(41 citation statements)

References 59 publications

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“…These findings suggest that oxidation of two of the three methionines within apoA-I causes a dramatic change in the conformation of the lipid-bound protein, with the N-terminal region becoming much more solvent exposed than in its native, unoxidized form (87). Recently Brock et al (88) reported that the methionine sulfoxide content of apoA-I was more abundant in the HDL of patients with type-1 diabetes, a disease for which cardiovascular events are a more significant complication, than in control patients.…”

Section: Methionine Oxidation Alters N-and C-termini Of Lipid-free Anmentioning

confidence: 99%

Three-dimensional models of HDL apoA-I: implications for its assembly and function

Thomas

Bhat

Sorci‐Thomas

2008

Journal of Lipid Research

109

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The purpose of this review is to highlight recent advances toward the refinement of a three-dimensional structure for lipid-bound apolipoprotein A-I (apoA-I) on recombinant HDL. Recently, X-ray crystallography has yielded a new structure for full-length, lipid-free apoA-I. Although this approach has not yet been successful in solving the threedimensional structure of lipid-bound apoA-I, analysis of the X-ray structures has been of immense help in the interpretation of structural data obtained from other methods that yield structural information. Recent studies emphasize the use of mass spectrometry to unambiguously identify crosslinked peptides or to quantify solvent accessibility using hydrogen-deuterium exchange. The combination of mass spectrometry, molecular modeling, molecular dynamic analysis, and small-angle X-ray diffraction has provided additional structural information on apoA-I folding that complements previous approaches. To understand the mechanism of HDL apolipoprotein A-I (apoA-I) protection against the development of coronary heart disease, recent investigations have focused on apoA-Iʼs dual functions in promoting lipid efflux (1-4) and its role in modulating immune cell activation (5-10). Recent attention has now focused on elucidating the threedimensional conformation of apoA-I, the most abundant protein constituent within the HDL particle, in response to its acquisition of phospholipid and cholesterol to form nascent lipoprotein particles.ApoA-I is a 28 kDa protein synthesized by the liver and small intestine. It plays a key role in the formation, metabolism, and catabolism of HDL, a plasma lipoprotein whose levels are highly linked to protection against the development of coronary artery disease, even in patients with very low LDL cholesterol levels (11). Formation of plasma HDL particles depends entirely on the initial lipidation of apoA-I by ABCA1 (12-14). Dimers of lipid-free or lipid-poor apoA-I acquire limited amounts of phospholipid and cholesterol from the membrane-bound ABCA1 transporter to form one of several classes of nascent HDL particles (15). Other classes of nascent HDL particles formed from this interaction contain more than two molecules of apoA-I per particle, with increased amounts of phospholipid and cholesterol (16)(17)(18).A second lipidation step essential for plasma HDL maturation is the activation of the enzyme LCAT by lipid-bound apoA-I. Activation of this enzyme results in the synthesis of cholesteryl esters on nascent HDL (19), providing a hydrophobic core and transforming the small, lipid-poor particle to a spherical lipid-rich HDL. Studies of human deficiencies have shown that if either ABCA1 or LCAT are inactive, plasma concentrations of HDL apoA-I are very low, owing to the rapid removal of the small lipid-poor HDL apoA-I from circulation (20,21). Thus, both of these two major apoA-I lipidation steps are absolutely essential for the formation of mature spherical plasma HDL and, to some extent, the functionality of the HDLs themselves (22-24).ApoA-I has...

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Section: Methionine Oxidation Alters N-and C-termini Of Lipid-free Anmentioning

confidence: 99%

Three-dimensional models of HDL apoA-I: implications for its assembly and function

Thomas

Bhat

Sorci‐Thomas

2008

Journal of Lipid Research

109

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“…For example, methionine sulfoxide [Met(O)], has been detected in circulating HDL of humans (20), and reactive intermediates are implicated in impairment of LCAT activity (21)(22)(23)(24)(25). Moreover, it was recently shown that the Met(O) content of apoA-I is elevated in human type 1 diabetes, a disorder strongly associated with increased levels of oxidative stress (26). Because a single Met residue, Met-148, lies in the LCAT activation domain of apoA-I (27), we investigated the role of Met oxidation in the loss of LCAT activity that occurs when MPO oxidizes apoA-I.…”

mentioning

confidence: 99%

Methionine oxidation impairs reverse cholesterol transport by apolipoprotein A-I

Shao

Cavigiolio²,

Brot

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

166

167

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“…Simi-larly, apoA-I containing methionine residues 86 and 112 as MetO (hereafter referred to as apoA-I 132 ) has been detected in circulating HDL, and is present at increased concentrations in subjects with a genotype associated with increased coronary artery disease (16). Moreover, it was recently shown that the MetO content of apoA-I is elevated in human type 1 diabetes (17), a disorder commonly associated with increased oxidative stress (18).…”

mentioning

confidence: 99%

A sensitive and specific ELISA detects methionine sulfoxide-containing apolipoprotein A-I in HDL

Wang

Shao

Oda³

et al. 2009

Journal of Lipid Research

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Oxidized HDL has been proposed to play a key role in atherogenesis. A wide range of reactive intermediates oxidizes methionine residues to methionine sulfoxide (MetO) in apolipoprotein A-I (apoA-I), the major HDL protein. These reactive species include those produced by myeloperoxidase, an enzyme implicated in atherogenesis. The aim of the present study was to develop a sensitive and specific ELISA for detecting MetO residues in HDL. We therefore immunized mice with HPLC-purified human apoA-I containing MetO 86 and MetO 112 (termed apoA-I 132 ) to generate a monoclonal antibody termed MOA-I. An ELISA using MOA-I detected lipid-free apoA-I 132 , apoA-I modified by 2e-oxidants (hydrogen peroxide, hypochlorous acid, peroxynitrite), and HDL oxidized by 1e-or 2e-oxidants and present in buffer or human plasma. Detection was concentration dependent, reproducible, and exhibited a linear response over a physiologically plausible range of concentrations of oxidized HDL. In contrast, MOA-I failed to recognize native apoA-I, native apoA-II, apoA-I modified by hydroxyl radical or metal ions, or LDL and methionine-containing proteins other than apoA-I modified by 2e-oxidants. Because the ELISA we have developed specifically detects apoA-I containing MetO in HDL and plasma, it should provide a useful tool for investigating the relationship between oxidized HDL and coronary artery disease.-Wang, X. S., B.

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Increased methionine sulfoxide content of apoA-I in type 1 diabetes

Cited by 44 publications

References 59 publications

Three-dimensional models of HDL apoA-I: implications for its assembly and function

Three-dimensional models of HDL apoA-I: implications for its assembly and function

Methionine oxidation impairs reverse cholesterol transport by apolipoprotein A-I

A sensitive and specific ELISA detects methionine sulfoxide-containing apolipoprotein A-I in HDL

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