TY - JOUR AU - Mróz, D.* AU - Wyszkowski, H.* AU - Szablewski, T.* AU - Zawieracz, K.* AU - Dutkiewicz, R.* AU - Bury, K.* AU - Wortmann, S.B. AU - Wevers, R.A.* AU - Zietkiewicz, S.* C1 - 57863 C2 - 48146 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - CLPB (caseinolytic peptidase B homolog), the first mitochondrial protein refoldase associated with human disease. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1864 IS - 4 PB - Elsevier PY - 2020 SN - 0304-4165 ER - TY - JOUR AB - Background: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. Methods: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed. Results: The overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites. Conclusion: Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures. General significance: An epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation. AU - Wahl, A. AU - Kasela, S.* AU - Monotoro, E.C.* AU - van Iterson, M.* AU - Štambuk, J.* AU - Sharma, S. AU - van den Akker, E.* AU - Klaric, L.* AU - Benedetti, E. AU - Razdorov, G.* AU - Trbojević-Akmačić, I.* AU - Vučković, F.* AU - Ugrina, I.* AU - Beekman, M.* AU - Deelen, J.* AU - van Heemst, D.* AU - Heijmans, B.T.* AU - Benedetti, E. AU - Wuhrer, M.* AU - Plomp, R.* AU - Keser, T.* AU - Šimurina, M.* AU - Pavić, T.* AU - Gudelj, I.* AU - Krištić, J.* AU - Grallert, H. AU - Kunze, S. AU - Peters, A. AU - Bell, J.T.* AU - Spector, T.D.* AU - Milani, L.* AU - Eline Slagboom, P.* AU - Lauc, G.* AU - Gieger, C. C1 - 52176 C2 - 43824 CY - Amsterdam SP - 637-648 TI - IgG glycosylation and DNA methylation are interconnected with smoking. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1862 IS - 3 PB - Elsevier Science Bv PY - 2018 SN - 0304-4165 ER - TY - JOUR AB - BACKGROUND: Statins are among the most widely prescribed medications worldwide and usually many individuals involved in clinical and population studies are on statin therapy. Immunoglobulin G (IgG) glycosylation has been associated with numerous cardiometabolic risk factors. METHODS: The aim of this study was to investigate the possible association of statin use with N-glycosylation of IgG. The association was analyzed in two large population cohorts (TwinsUK and KORA) using hydrophilic interaction liquid chromatography (HILIC-UPLC) in the TwinsUK cohort and reverse phase liquid chromatography coupled with electrospray mass spectrometry (LC-ESI-MS) in the KORA cohort. Afterwards we investigated the same association for only one statin (rosuvastatin) in a subset of individuals from the randomized double-blind placebo-controlled JUPITER study using LC-ESI-MS for IgG glycome and HILIC-UPLC for total plasma N-glycome. RESULTS: In the TwinsUK population, the use of statins was associated with higher levels of core-fucosylated biantennary glycan structure with bisecting N-acetylglucosamine (FA2B) and lower levels of core-fucosylated biantennary digalactosylated monosialylated glycan structure (FA2G2S1). The association between statin use and FA2B was replicated in the KORA cohort. In the JUPITER trial we found no statistically significant differences between the randomly allocated placebo and rosuvastatin groups. CONCLUSIONS: In the TwinsUK and KORA cohorts, statin use was associated with a small increase of pro-inflammatory IgG glycan, although this finding was not confirmed in a subset of participants from the JUPITER trial. GENERAL SIGNIFICANCE: Even if the association between IgG N-glycome and statins exists, it is not large enough to pose a problem for glycomic studies. AU - Keser, T.* AU - Vučković, F.* AU - Barrios, C.* AU - Zierer, J. AU - Wahl, A. AU - Akinkuolie, A.O.* AU - Stambuk, J.* AU - Nakić, N.* AU - Pavić, T.* AU - Periša, J.* AU - Mora, S.* AU - Gieger, C. AU - Menni, C.* AU - Spector, T.D.* AU - Gornik, O.* AU - Lauc, G.* C1 - 50614 C2 - 42565 CY - Amsterdam SP - 1152-1158 TI - Effects of statins on the immunoglobulin G glycome. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1861 IS - 5 PB - Elsevier Science Bv PY - 2017 SN - 0304-4165 ER - TY - JOUR AB - BACKGROUND: During maturation and storage, spermatozoa generate substantial amounts of reactive oxygen species (ROS) and are thus forced to cope with an increasing oxidative environment that is both needed and detrimental to their biology. Such a janus-faceted intermediate needs to be tightly controlled and this is done by a wide array of redox enzymes. These enzymes not only have to prevent unspecific modifications of essential cellular biomolecules by quenching undesired ROS, but they are required and often directly involved in critical protein modifications. SCOPE OF REVIEW: The present review is conceived to present an update on what is known about critical roles of redox enzymes, whereby special emphasis is put on the family of glutathione peroxidases, which for the time being present the best characterized tasks during gametogenesis. MAJOR CONCLUSIONS: We therefore demonstrate that understanding the function of (seleno)thiol-based oxidases/reductases is not a trivial task and relevant knowledge will be mainly gained by using robust systems, as exemplified by several (conditional) knockout studies. We thus stress the importance of using such models for providing unequivocal evidence in the molecular understanding of redox regulatory mechanisms in sperm maturation. GENERAL SIGNIFICANCE: ROS are not only detrimental by-products of metabolism and its proper generation and usage by specific enzymes is essential for vital functions as beautifully exemplified during male gametogenesis. As such, lessons learnt from thiol-based oxidases/reductases in male gametogenesis could be used as a general principle for other organs as it is most likely not only restricted to this developmental phase. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. AU - Conrad, M. AU - Ingold, I. AU - Buday, K. AU - Kobayashi, S. AU - Friedmann Angeli, J.P.F. C1 - 42894 C2 - 35734 CY - Amsterdam SP - 1566-1574 TI - ROS, thiols and thiol-regulating systems in male gametogenesis. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1850 IS - 8 PB - Elsevier Science Bv PY - 2015 SN - 0304-4165 ER - TY - JOUR AB - BACKGROUND: Mammalian GPx7 is a monomeric glutathione peroxidase of the endoplasmic reticulum (ER), containing a Cys redox center (CysGPx). Although containing a peroxidatic Cys (CP) it lacks the resolving Cys (CR), that confers fast reactivity with thioredoxin (Trx) or related proteins to most other CysGPxs. METHODS: Reducing substrate specificity and mechanism were addressed by steady-state kinetic analysis of wild type or mutated mouse GPx7. The enzymes were heterologously expressed as a synuclein fusion to overcome limited expression. Phospholipid hydroperoxide was the oxidizing substrate. Enzyme-substrate and protein-protein interaction were analyzed by molecular docking and surface plasmon resonance analysis. RESULTS: Oxidation of the CP is fast (k+1>10(3)M(-1)s(-1)), however the rate of reduction by GSH is slow (k'+2=12.6M(-1)s(-1)) even though molecular docking indicates a strong GSH-GPx7 interaction. Instead, the oxidized CP can be reduced at a fast rate by human protein disulfide isomerase (HsPDI) (k+1>10(3)M(-1)s(-1)), but not by Trx. By surface plasmon resonance analysis, a KD=5.2μM was calculated for PDI-GPx7 complex. Participation of an alternative non-canonical CR in the peroxidatic reaction was ruled out. Specific activity measurements in the presence of physiological reducing substrate concentration, suggest substrate competition in vivo. CONCLUSIONS: GPx7 is an unusual CysGPx catalyzing the peroxidatic cycle by a one Cys mechanism in which GSH and PDI are alternative substrates. GENERAL SIGNIFICANCE: In the ER, the emerging physiological role of GPx7 is oxidation of PDI, modulated by the amount of GSH. AU - Bosello-Travain, V.* AU - Conrad, M. AU - Cozza, G.* AU - Negro, A.* AU - Quartesan, S.* AU - Rossetto, M.* AU - Roveri, A.* AU - Toppo, S.* AU - Ursini, F.* AU - Zaccarin, M.* AU - Maiorino, M.* C1 - 24370 C2 - 31503 SP - 3846-3857 TI - Protein disulfide isomerase and glutathione are alternative substrates in the one Cys catalytic cycle of glutathione peroxidase 7. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1830 IS - 6 PB - Elsevier PY - 2013 SN - 0304-4165 ER - TY - JOUR AB - Selenium, as an integral part of selenoproteins, is essential for mammals. Unequivocal evidence had been provided more than a decade ago when it was proven that mice incapable of producing any of the 24 selenoproteins failed to develop beyond the gastrulation stage (E6.5). Since then, more specific attempts have been made to unmask novel and essential functions of individual selenoproteins in mice. Genetic disruption of glutathione peroxidase 4 (GPx4; also referred to as phospholipid hydroperoxide glutathione peroxidase, PHGPx) in mice showed for the first time that a specific selenoenzyme is in fact required for early embryonic development. Later on, systemic ablation of cytosolic thioredoxin reductase (Txnrd1) or mitochondrial thioredoxin reductase (Txnrd2) yielded embryonic lethal phenotypes. Beside those three, no other selenoproteins have been found being indispensable for murine development so far. This review aims at summarizing mainly the in vivo findings on these important mammalian selenoenzymes, which have not only common attributes of being required for embryogenesis, but that they are also instrumental in the regulation of cellular redox metabolism. AU - Conrad, M. C1 - 1941 C2 - 27084 CY - Amsterdam SP - 1575-1585 TI - Transgenic mouse models for the vital selenoenzymes cytosolic thioredoxin reductase, mitochondrial thioredoxin reductase and glutathione peroxidase 4. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1790 IS - 11 PB - Elsevier PY - 2009 SN - 0304-4165 ER - TY - JOUR AU - Bors, W. AU - Michel, C. AU - Stettmaier, K. AU - Lu, Y.* AU - Foo, L.Y.* C1 - 10338 C2 - 20836 SP - 97-107 TI - Pulse radiolysis, electron paramagnetic resonance spectroscopy and theoretical calculations of caffeic acid oligomer radicals. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1620 PY - 2003 SN - 0304-4165 ER - TY - JOUR AU - Navakoudis, E.* AU - Lütz, C.* AU - Langebartels, C. AU - Lütz-Meindl, U.* AU - Kotzabasis, K.* C1 - 22251 C2 - 21013 SP - 160-169 TI - Ozone impact on the photosynthetic apparatus and the protective role of polyamines. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 1621 PY - 2003 SN - 0304-4165 ER - TY - JOUR AB - Transient spectra and kinetic data of Tiron (1,2-dihydroxybenzene-3,5-disulphonic acid) are reported, obtained after pulse-radiolytic oxidation by hydroxyl radicals ({ring operator}OH), superoxide anions (O2 -) or a combination of both oxygen radicals. The rate constant with {ring operator}OH radicals was determined at 1.0·109 M-1·s-1. Contrary to a previous report (Greenstock, C.L. and Miller, R.W. (1975) Biochim. Biophys. Acta 396, 11-16), the rate constant with O2 - of 1.0·107 M-1·s-1 is lower by one order of magnitude; also the semiquinone absorbs at 300 nm rather than at 400 nm. The ratio of the rate constants with {ring operator}OH and O2 - of 100 again demonstrates that any oxidation reaction by the latter radical is unspecific due to the more efficient reaction of {ring operator}OH radicals, leading to the same products with catechol compounds. AU - Bors, W. AU - Saran, M. AU - Michel, C. C1 - 41466 C2 - 35760 SP - 537-542 TI - Pulse-radiolytic investigations of catechols and catecholamines II : Reactions of Tiron with oxygen radical species. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 582 IS - 3 PY - 1979 SN - 0304-4165 ER - TY - JOUR AB - The pure absorbance of turbid cell suspensions of various phototrophic microorganisms was determined by collecting the scattered light. A conventional spectrophotometer was used, equipped with an integrating sphere as receiver unit, which allowed precise measurements of the absorbance in the range from zero to 0.1. In the wavelength range 300-1100 nm, where photosynthesis occurs, light scattered only once by a bacterial cell retains predominantly the forward direction. This allows measurements of pure absorption, when the concentration of cells which the light has to pass through is small. For example, by comparison of measurements of pigmented and nonpigmented cell suspensions of Rhodopseudomonas acidophila, it was shown that the total sum of scattered light can be collected. The best results were obtained using cuvettes with a light path of 0.1 cm or 0.2 cm to measure cell suspensions of about 0.2 mg dry weight per ml. For R. acidophila this corresponds to 1-3 cell layers. Extinction-, absorbance- and scattering spectra for R. acidophila are presented, in addition to the absorbance spectra for Rhodospirillum rubrum, Aphanocapsa and Scenedesmus. AU - Göbel, F.D. C1 - 40955 C2 - 38518 SP - 593-602 TI - Direct measurement of pure absorbance spectra of living phototrophic microorganisms. JO - Biochim. Biophys. Acta-Gen. Subj. VL - 538 IS - 3 PY - 1978 SN - 0304-4165 ER -