4 research outputs found
Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort
INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals
Formation of Ternary Complexes with MgATP: Effects on the Detection of Mg<sup>2+</sup> in Biological Samples by Bidentate Fluorescent Sensors
Fluorescent indicators based on β-keto-acid
bidentate coordination motifs display superior metal selectivity profiles
compared to current <i>o</i>-aminophenol-<i>N</i>,<i>N</i>,<i>O</i>-triacetic acid (APTRA) based
chelators for the study of biological magnesium. These low denticity
chelators, however, may allow for the formation of ternary complexes
with Mg<sup>2+</sup> and common ligands present in the cellular milieu.
In this work, absorption, fluorescence, and NMR spectroscopy were
employed to study the interaction of turn-on and ratiometric fluorescent
indicators based on 4-oxo-4H-quinolizine-3-carboxylic acid with Mg<sup>2+</sup> and ATP, the most abundant chelator of biological magnesium,
thus revealing the formation of ternary complexes under conditions
relevant to fluorescence imaging. The formation of ternary species
elicits comparable or greater optical changes than those attributed
to the formation of binary complexes alone. Dissociation of the fluorescent
indicators from both ternary and binary species have apparent equilibrium
constants in the low millimolar range at pH 7 and 25 °C. These
results suggest that these bidentate sensors are incapable of distinguishing
between free Mg<sup>2+</sup> and MgATP based on ratio or intensity-based
steady-state fluorescence measurements, thus posing challenges in
the interpretation of results from fluorescence imaging of magnesium
in nucleotide-rich biological samples
Lipopolysaccharide-binding protein and future Parkinson’s disease risk: a European prospective cohort
Abstract Introduction Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson’s disease (PD) in small-scale retrospective case–control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case–control study within a large European prospective cohort. Methods A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. Results Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1–41.0) vs. 24.7 (16.6–38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98–2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40–5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09–2.18). Conclusion The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals