Atherosclerosis

1998

DOI: 10.1016/s0021-9150(98)00153-1

|View full text |Cite

|

Sign up to set email alerts

|

Association of malondialdehyde–acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury

¹

,

Joshua M. Miller

²

,

B. Timothy Baxter

³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Diet and Ethanol Intake2

P110␦ Activity Is Important For Normal Levels Of Circulating1

Discussion1

Citation Types

Supporting

2

Mentioning

78

Contrasting

0

Year Published

2000

2000

2015

2015

Publication Types

Select...

Article8

Other1

Relationship

Self Cite1

Independent8

Authors

Journals

Cited by 81 publications

(80 citation statements)

References 20 publications

Supporting

2

Mentioning

78

Contrasting

0

Order By: Relevance

“…6B and supplemental Fig. 3A), models of oxidation-specific epitopes found on LDL in atherosclerotic lesions (3,48). Serum titers of the germlineencoded T15/E06 IgM natural Ab, which recognizes the phosphocholine head group of oxidized phospholipids found in OxLDL (49,50), were also reduced in the p110␦ D910A KI mice (Fig.…”

Section: P110␦ Activity Is Important For Normal Levels Of Circulatingmentioning

confidence: 89%

Phosphoinositide 3-Kinase p110δ Regulates Natural Antibody Production, Marginal Zone and B-1 B Cell Function, and Autoantibody Responses

¹

,

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

B-1 and marginal zone (MZ) B cells produce natural Abs, make Ab responses to microbial pathogens, and contribute to autoimmunity. Although the δ isoform of the PI3K p110 catalytic subunit is essential for development of these innate-like B cells, its role in the localization, activation, and function of normal B-1 and MZ B cells is not known. Using IC87114, a highly selective inhibitor of p110δ enzymatic activity, we show that p110δ is important for murine B-1 and MZ B cells to respond to BCR clustering, the TLR ligands LPS and CpG DNA, and the chemoattractants CXCL13 and sphingosine 1-phosphate. In these innate-like B cells, p110δ activity mediates BCR-, TLR- and chemoattractant-induced activation of the Akt prosurvival kinase, chemoattractant-induced migration, and TLR-induced proliferation. Moreover, we found that TLR-stimulated Ab responses by B-1 and MZ B cells, as well as the localization of MZ B cells in the spleen, depend on p110δ activity. Finally, we show that the in vivo production of natural Abs requires p110δ and that p110δ inhibitors can reduce in vivo autoantibody responses. Thus, targeting p110δ may be a novel approach for regulating innate-like B cells and for treating Ab-mediated autoimmune diseases.

“…6B and supplemental Fig. 3A), models of oxidation-specific epitopes found on LDL in atherosclerotic lesions (3,48). Serum titers of the germlineencoded T15/E06 IgM natural Ab, which recognizes the phosphocholine head group of oxidized phospholipids found in OxLDL (49,50), were also reduced in the p110␦ D910A KI mice (Fig.…”

Section: P110␦ Activity Is Important For Normal Levels Of Circulatingmentioning

confidence: 89%

Phosphoinositide 3-Kinase p110δ Regulates Natural Antibody Production, Marginal Zone and B-1 B Cell Function, and Autoantibody Responses

¹

,

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

B-1 and marginal zone (MZ) B cells produce natural Abs, make Ab responses to microbial pathogens, and contribute to autoimmunity. Although the δ isoform of the PI3K p110 catalytic subunit is essential for development of these innate-like B cells, its role in the localization, activation, and function of normal B-1 and MZ B cells is not known. Using IC87114, a highly selective inhibitor of p110δ enzymatic activity, we show that p110δ is important for murine B-1 and MZ B cells to respond to BCR clustering, the TLR ligands LPS and CpG DNA, and the chemoattractants CXCL13 and sphingosine 1-phosphate. In these innate-like B cells, p110δ activity mediates BCR-, TLR- and chemoattractant-induced activation of the Akt prosurvival kinase, chemoattractant-induced migration, and TLR-induced proliferation. Moreover, we found that TLR-stimulated Ab responses by B-1 and MZ B cells, as well as the localization of MZ B cells in the spleen, depend on p110δ activity. Finally, we show that the in vivo production of natural Abs requires p110δ and that p110δ inhibitors can reduce in vivo autoantibody responses. Thus, targeting p110δ may be a novel approach for regulating innate-like B cells and for treating Ab-mediated autoimmune diseases.

“…This latter observation is of particular interest, because protein derivatization with high concentrations of MDA leads to the formation of substantial amounts of cyclic MAA adducts. 31 Some degree of reactivity against MAA-modified HSA can also be observed in patients with liver disease unrelated to alcohol abuse. However, the binding of these sera to MAA adducts is not affected by preadsorption with hexyl-MAA, indicating that the cyclic epitopes are not responsible for such reactivity, that is instead specific for the alcohol-related disease.…”

Section: Discussionmentioning

confidence: 99%

Detection of circulating antibodies against malondialdehyde-acetaldehyde adducts in patients with alcohol-induced liver disease

¹

,

²

,

³

et al. 2000

View full text Add to dashboard Cite

Acetaldehyde and malonildialdehyde can form hybrid protein adducts, named MAA adducts that have strong immunogenic properties. The formation of MAA adducts in the liver of chronic alcohol-fed rats is associated with the development of circulating antibodies that specifically recognized these adducts. The aim of this study was to examine whether MAA adducts might participate in the immune response associated with human alcohol-induced liver disease. Circulating antibodies against MAA adducts were evaluated in 50 patients with alcohol-induced hepatitis or cirrhosis, in 40 patients with non-alcohol-induced liver disease, in 15 heavy drinkers without liver damage and in 40 healthy controls by enzyme-linked immunosorbent assays (ELISA). Immunoglobulin G (IgG) reacting with MAA-modified proteins were significantly increased in the patients with alcohol-induced cirrhosis or hepatitis. The individual levels of anti-MAA IgG in those patients were associated with the severity of liver damage. Anti-MAA antibodies were also positively correlated with the levels of IgG recognizing epitopes generated by acetaldehyde and malonildialdehyde. However, competitive inhibition experiments indicated that the anti-MAA antibodies were unrelated to those against acetaldehyde-or malonildialdehydederived antigens and mainly recognized a specific, cyclic MAA epitope. Some degree of immune reactivity towards MAA adducts was also observed in patients with nonalcohol-induced liver injury. However, competitive ELISA showed that the antigens recognized by these sera were not the cyclic MAA adducts. Altogether, these results showed the formation of MAA antigens during alcohol-induced liver disease and suggest their possible contribution to the development of immunologic reactions associated with alcohol-related liver damage. (HEPATOLOGY 2000;31:878-884.)

“…3 It also produces a large family of ␥-ketoaldehydes (␥KA), regioisomers that have been given the trivial name of isoketals or isolevuglandins. Exposure of vascular cells to various aldehydes results in endothelial dysfunction, secretion of cytokines, and recruitment of monocytes (1)(2)(3)(4)(5)(6)(7), all of which are key steps in the initiation of the chronic inflammatory conditions leading to atherosclerosis.…”

mentioning

confidence: 99%

Phosphatidylethanolamines Modified by γ-Ketoaldehyde (γKA) Induce Endoplasmic Reticulum Stress and Endothelial Activation

¹

,

Chen²,

Cox³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Peroxidation of plasma lipoproteins has been implicated in the endothelial cell activation and monocyte adhesion that initiate atherosclerosis, but the exact mechanisms underlying this activation remain unclear. Lipid peroxidation generates lipid aldehydes, including the ␥-ketoaldehydes (␥KA), also termed isoketals or isolevuglandins, that readily modify the amine headgroup of phosphatidylethanolamine (PE). We hypothesized that aldehyde modification of PE could mediate some of the proinflammatory effects of lipid peroxidation. We found that PE modified by ␥KA (␥KA-PE) induced THP-1 monocyte adhesion to human umbilical cord endothelial cells. ␥KA-PE also induced expression of adhesion molecules and increased MCP-1 and IL-8 mRNA in human umbilical cord endothelial cells. To determine the structural requirements for ␥KA-PE activity, we tested several related compounds. PE modified by 4-oxo-pentanal induced THP-1 adhesion, but N-glutaroyl-PE and C 18:0 N-acyl-PE did not, suggesting that an N-pyrrole moiety was essential for cellular activity. As the N-pyrrole headgroup might distort the membrane, we tested the effect of the pyrrolePEs on membrane parameters. ␥KA-PE and 4-oxo-pentanal significantly reduced the temperature for the liquid crystalline to hexagonal phase transition in artificial bilayers, suggesting that these pyrrole-PE markedly altered membrane curvature. Additionally, fluorescently labeled ␥KA-PE rapidly internalized to the endoplasmic reticulum (ER); ␥KA-PE induced C/EBP homologous protein CHOP and BiP expression and p38 MAPK activity, and inhibitors of ER stress reduced ␥KA-PE-induced C/EBP homologous protein CHOP and BiP expression as well as EC activation, consistent with ␥KA-PE inducing ER stress responses that have been previously linked to inflammatory chemokine expression. Thus, ␥KA-PE is a potential mediator of the inflammation induced by lipid peroxidation.Lipid peroxidation has been implicated in a host of pathological processes, including inflammation and atherosclerosis, but there is still much that is unknown about the mechanisms linking lipid peroxidation to the activation of inflammatory responses. Lipid peroxidation produces a plethora of lipid aldehydes ( Fig. 1), including malondialdehyde, acrolein, and 4-hydroxynonenal (HNE).3 It also produces a large family of ␥-ketoaldehydes (␥KA), regioisomers that have been given the trivial name of isoketals or isolevuglandins. Exposure of vascular cells to various aldehydes results in endothelial dysfunction, secretion of cytokines, and recruitment of monocytes (1-7), all of which are key steps in the initiation of the chronic inflammatory conditions leading to atherosclerosis.Despite these potentially important inflammatory effects, the mechanisms whereby lipid aldehydes induce their effects on vascular cells are still poorly understood. Significant effort has focused on the effects of protein and DNA modification by lipid aldehydes. However, recent studies have shown that lipid aldehydes, including malondialdehyde, acrolein, HNE, and ␥KA, a...

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Product

Browser Extension Assistant by scite Citation Statement Search Reference Check Visualizations Dashboards Explore Journals Explore Organizations Explore Funders Embedding Badge Embedding Citation Search Pricing

Resources

Blog Help & FAQ Accessibility Statement API Terms For Universities & Governments For Researchers For Publishers For Corporate, Pharma & Enterprise Author Marketing Become an Affiliate Get an organization trial or quote scite Data & Services

About

News & Press Careers Read our Paper Coverage

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Copyright © 2024 scite LLC. All rights reserved.

Made with 💙 for researchers

Part of the Research Solutions Family.