Effects of hyperoxia and cardiovascular risk factors on myocardial ischaemia-reperfusion injury: a randomized, sham-controlled parallel study.

peer reviewedThe beneficial effects of supplemental oxygen in patients with acute myocardial infarction are still uncertain: what are the effects of ischaemia-reperfusion injury during hyperoxia and normoxia in mature rats with and without cardiovascular risk factors? What is the main finding and its importance? Despite elevated baseline oxidative stress in rodents with cardiovascular risk factors, hyperoxic reperfusion limited myocardial necrosis and anti/pro-oxidant imbalance in spontaneously hypertensive and Zucker rats. In contrast, this effect was exacerbated in healthy Wistar rats. These results suggest that oxygen supplementation may not be harmful in patients with acute myocardial injury. ABSTRACT: Recent studies on O2 supplementation in acute coronary syndrome patients are equivocal. We tested the hypothesis that oxidative stress is increased in rodents with cardiovascular risk factors and enhances ischaemia-reperfusion injury in the presence of hyperoxia. A total of 43 Wistar rats (WR), 30 spontaneously hypertensive rats (SHR) and 33 obese Zucker rats (ZR) were randomized in a sham procedure (one-third) or underwent a left anterior descending ligation of the coronary artery for 60 min (two-thirds). This was followed by 3 h of reperfusion while animals were randomized either in a hyperoxic (HR) or a normoxic reperfusion (NR) group. Myocardial infarction size and oxidative stress biomarkers (myeloperoxidase (MPO), malondialdehyde and total free thiols) were assessed in blood samples. Baseline troponin T was higher in SHR and ZR than in WR (both P < 0.001). Baseline total MPO was elevated in ZR in comparison to SHR and WR (both P < 0.001). SHR had lower thiol concentration compared to WR and ZR (P < 0.000001). HR was associated with a lower troponin T rise in SHR and ZR than in NR (both P < 0.001), while the reverse occurred in WR (P < 0.001). In SHR, HR limited total MPO increase as compared to NR (P = 0.0056) and the opposite effect was observed with total MPO in WR (P = 0.013). NR was associated with a drastic reduction of total thiols as compared to HR both in SHR and in ZR (both P < 0.001). Despite a heightened baseline oxidative stress level, HR limited myocardial necrosis and anti/pro-oxidant imbalance in SHR and ZR whereas this effect was exacerbated in healthy WR

The Pyla-1 Natural Accession of Arabidopsis thaliana Shows Little Nitrate-Induced Plasticity of Root Development

Optimizing root system architecture is a strategy for coping with soil fertility, such as low nitrogen input. An ample number of Arabidopsis thaliana natural accessions have set the foundation for studies on mechanisms that regulate root morphology. This report compares the Columbia-0 (Col-0) reference and Pyla-1 (Pyl-1) from a coastal zone in France, known for having the tallest sand dune in Europe. Seedlings were grown on vertical agar plates with different nitrate concentrations. The lateral root outgrowth of Col-0 was stimulated under mild depletion and repressed under nitrate enrichment. The Pyl-1 produced a long primary root and any or very few visible lateral roots across the nitrate supplies. This could reflect an adaptation to sandy soil conditions, where the primary root grows downwards to the lower strata to take up water and mobile soil resources without elongating the lateral roots. Microscopic observations revealed similar densities of lateral root primordia in both accessions. The Pyl-1 maintained the ability to initiate lateral root primordia. However, the post-initiation events seemed to be critical in modulating the lateral-root-less phenotype. In Pyl-1, the emergence of primordia through the primary root tissues was slowed, and newly formed lateral roots stayed stunted. In brief, Pyl-1 is a fascinating genotype for studying the nutritional influences on lateral root development.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Optimisation of parameters to improve protein sequence recovery by LC-MS/MS: application to apolipoprotein B-1000 and myeloperoxidase

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Oxidation of Apolipoprotein-B-100: a Proteomic Approach of Atherosclerosis

Atherosclerosis is an inflammatory disease characterized by the accumulation of lipids in the subendothelial space. Among the proatherogenic factors, the oxidative modifications of low-density lipoproteins (LDLs) are frequently mentioned. Apolipoprotein-B-100 (ApoB100) is the major protein of LDLs which stabilizes the particle, binds to the LDL receptor and plays a key role in lipoprotein metabolism. It is also a huge protein (550kDa) containing 4536 amino acids. Although many experiments have been done on copper-oxidized LDLs, other more physiological pathways of oxidation are known and myeloperoxidase (MPO) is one of them (1). MPO is indeed able to oxidize ApoB100 by catalysing the synthesis of hypochlorous acid (HOCl), a powerful oxidant, in the presence of hydrogen peroxide (H2O2) and chloride ions (2). However, the oxidative modifications of ApoB100 are still unclear. In order to determine characteristics of the specific MPO-dependent oxidation, we analyzed in vitro modifications of ApoB100 under 2 oxidative conditions: the oxidation of native-LDLs with (i) HOCl (to mimic MPO-oxidation), and (ii) the MPO/H2O2/Cl- system. ApoB100 was isolated from LDLs, digested using trypsin and the resulting peptides were analyzed by LC-autoMS/MS. As ApoB100 is a large protein, we optimized numbers of parameters involved in the analytical method and the data analyses, in order to increase the sequence coverage (79% instead of 50% in the literature) and to detect a maximum of modifications(3). The three major residues targeted by oxidative species were methionine, tryptophan and tyrosine, forming methionine sulfoxide, hydroxy-tryptophan and chloro-tyrosine, respectively. Although similar oxidized residues were detected in both conditions, several amino acids were specifically oxidized by MPO: 2 tyrosine residues (Y76 and Y1901) and some methionine residues (M723, M727, M1080, M1715, M1716 and M3986). ApoB100 modifications are therefore different under both experimental conditions, revealing important characteristics of the specific MPO-dependent oxidation, a physiologically relevant process. The MPO site-specific oxidations will be further examined in patients who present different clinical situations. (1) Daugherty and Roselaar, Cardiovascular Research 29 (1995). (2) Klebanoff, J Leukoc Biol 77 (2005). (3) Delporte et al. J. Anal. Biochem. 411 (2011).info:eu-repo/semantics/nonPublishe

DEVELOPMENT OF AN ANALYTICAL METHOD USING LC/MSMS TO QUANTIFY OXO(d)GUANOSINE AND CHLOROGUANOSINE IN URINE

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Low-density lipoproteins are directly or indirectly carbamylated by myeloperoxidase

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Effects of hyperoxia and cardiovascular risk factors on myocardial ischaemia-reperfusion injury :a randomized, sham-controlled parallel study

info:eu-repo/semantics/publishe

Proteomic and metabolomic analyses at the Institute of Pharmacy - Optimization of Parameters to Improve Protein Sequence Recovery by LC-MS/MS: Applications to Apolipoprotein-B-100 and Myeloperoxidase.

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Specific oxidation of apolipoprotein B-100 by Myeloperoxidase

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