Linked Life Data

19887391

Source:http://linkedlifedata.com/resource/pubmed/id/19887391

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-19
pubmed:abstractText
The adipose tissue hormone leptin and homocysteine (Hcy)-thiolactone are linked to the pathogenesis of atherosclerosis through their interactions with the anti-atherogenic enzyme paraoxonase 1 that has the ability to hydrolyze Hcy-thiolactone and minimizes protein N-homocysteinylation. Here we examined the relationships between hyperleptinemia, Hcy-thiolactonase, and protein N-homocysteinylation in rats. Hyperleptinemia was induced in adult rats by administration of leptin for 7 days (0.25 mg/kg twice daily s.c). We found that serum Hcy-thiolactonase was lower in hyperleptinemic than in control animals (-41.0%, P<0.001). Leptin administration increased the level of N-linked Hcy in plasma proteins (+92.9%, P<0.01), but had no effect on plasma total Hcy. These effects were not reproduced by pair-feeding. We also found that the synthetic liver X receptor (LXR) agonist, T0901317 (1 mg/kg per day) normalized Hcy-thiolactonase and protein N-homocysteinylation levels in leptin-treated rats. However, leptin-induced increase in plasma isoprostane levels (a marker of oxidative stress) was not normalized by T0901317. The NADPH oxidase inhibitor apocynin prevented leptin-induced increase in isoprostane levels but did not normalize Hcy-thiolactonase and protein N-homocysteinylation levels. These results suggest that the decreased capacity to metabolize Hcy-thiolactone and concomitant increase in protein N-homocysteinylation contribute to pro-atherogenic effect of chronic hyperleptinemia, independently of oxidative stress. LXR agonists normalize Hcy-thiolactonase levels and decrease protein N-homocysteinylation, especially under conditions associated with excess leptin such as metabolic syndrome.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acetophenones, http://linkedlifedata.com/resource/pubmed/chemical/Aryldialkylphosphatase, http://linkedlifedata.com/resource/pubmed/chemical/Blood Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Homocysteine, http://linkedlifedata.com/resource/pubmed/chemical/Hydrocarbons, Fluorinated, http://linkedlifedata.com/resource/pubmed/chemical/Leptin, http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase, http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/TO-901317, http://linkedlifedata.com/resource/pubmed/chemical/acetovanillone, http://linkedlifedata.com/resource/pubmed/chemical/homocysteine thiolactone, http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1479-6805
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
204
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Modulation of paraoxonase 1 and protein N-homocysteinylation by leptin and the synthetic liver X receptor agonist T0901317 in the rat.
pubmed:affiliation
Department of Pathophysiology, Medical University, 20-090 Lublin, Poland. jerzy.beltowski@am.lublin.pl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't