Dataset Information

VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC.

ABSTRACT: High levels of circulating lipoprotein constitute a risk factor for cardiovascular diseases, and in this context, the specific role of the very-low-density lipoproteins (VLDL) is poorly understood. The response of human umbilical vein endothelial cells (HUVEC) to VLDL exposure was studied, especially focusing on the pathways involved in alteration of redox homeostasis and nitric oxide (NO) bioavailability. The results obtained by the analysis of the expression level of genes implicated in the NO metabolism and oxidative stress response indicated a strong activation of inducible NO synthase (iNOS) upon 24?h exposure to VLDL, particularly if these have been preventively oxidised. Simultaneously, both mRNA and protein expression of endothelial NO synthase (eNOS) were decreased and its phosphorylation pattern, at the key residues Tyr495 and Ser1177, strongly suggested the occurrence of the eNOS uncoupling. The results are consistent with the observed increased production of nitrites and nitrates (NOx), reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), and, at mitochondrial level, a deficit in mitochondrial O2 consumption. Altogether, these data suggest that the VLDL, particularly if oxidised, when allowed to persist in contact with endothelial cells, strongly alter NO bioavailability, affecting redox homeostasis and mitochondrial function.

SUBMITTER: Magnifico MC

PROVIDER: S-EPMC5632467 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC.

Magnifico Maria Chiara MC Oberkersch Roxana Elena RE Mollo Azzurra A Giambelli Luca L Grooten Yasmine Y Sarti Paolo P Calabrese Graciela Cristina GC Arese Marzia M

Oxidative medicine and cellular longevity 20170920

High levels of circulating lipoprotein constitute a risk factor for cardiovascular diseases, and in this context, the specific role of the very-low-density lipoproteins (VLDL) is poorly understood. The response of human umbilical vein endothelial cells (HUVEC) to VLDL exposure was studied, especially focusing on the pathways involved in alteration of redox homeostasis and nitric oxide (NO) bioavailability. The results obtained by the analysis of the expression level of genes implicated in the NO ...[more]

PMID: 29085553

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Project description:A series of tetranuclear iron complexes displaying a site-differentiated metal center was synthesized. Three of the metal centers are coordinated to our previously reported ligand, based on a 1,3,5-triarylbenzene motif with nitrogen and oxygen donors. The fourth (apical) iron center is coordinatively unsaturated and appended to the trinuclear core through three bridging pyrazolates and an interstitial μ4-oxide moiety. Electrochemical studies of complex [LFe3(PhPz)3OFe][OTf]2 revealed three reversible redox events assigned to the Fe(II)4/Fe(II)3Fe(III) (-1.733 V), Fe(II)3Fe(III)/Fe(II)2Fe(III)2 (-0.727 V), and Fe(II)2Fe(III)2/Fe(II)Fe(III)3 (0.018 V) redox couples. Combined Mössbauer and crystallographic studies indicate that the change in oxidation state is exclusively localized at the triiron core, without changing the oxidation state of the apical metal center. This phenomenon is assigned to differences in the coordination environment of the two metal sites and provides a strategy for storing electron and hole equivalents without affecting the oxidation state of the coordinatively unsaturated metal. The presence of a ligand-binding site allowed the effect of redox modulation on nitric oxide activation by an Fe(II) metal center to be studied. Treatment of the clusters with nitric oxide resulted in binding of NO to the apical iron center, generating a {FeNO}(7) moiety. As with the NO-free precursors, the three reversible redox events are localized at the iron centers distal from the NO ligand. Altering the redox state of the triiron core resulted in significant change in the NO stretching frequency, by as much as 100 cm(-1). The increased activation of NO is attributed to structural changes within the clusters, in particular, those related to the interaction of the metal centers with the interstitial atom. The differences in NO activation were further shown to lead to differential reactivity, with NO disproportionation and N2O formation performed by the more electron-rich cluster.

Project description:BackgroundMelatonin is a pleiotropic signaling molecule that plays multifarious roles in plants stress tolerance. The polyamine (PAs) metabolic pathway has been suggested to eliminate the effects of environmental stresses. However, the underlying mechanism of how melatonin and PAs function together under heat stress largely remains unknown. In this study, we investigated the potential role of melatonin in regulating PAs and nitric oxide (NO) biosynthesis, and counterbalancing oxidative damage induced by heat stress in tomato seedlings.ResultsHeat stress enhanced the overproduction of reactive oxygen species (ROS) and damaged inherent defense system, thus reduced plant growth. However, pretreatment with 100??M melatonin (7?days) followed by exposure to heat stress (24?h) effectively reduced the oxidative stress by controlling the overaccumulation of superoxide (O2•-) and hydrogen peroxide (H2O2), lowering the lipid peroxidation content (as inferred based on malondialdehyde content) and less membrane injury index (MII). This was associated with increased the enzymatic and non-enzymatic antioxidants activities by regulating their related gene expression and modulating the ascorbate-glutathione cycle. The presence of melatonin induced respiratory burst oxidase (RBOH), heat shock transcription factors A2 (HsfA2), heat shock protein 90 (HSP90), and delta 1-pyrroline-5-carboxylate synthetase (P5CS) gene expression, which helped detoxify excess ROS via the hydrogen peroxide-mediated signaling pathway. In addition, heat stress boosted the endogenous levels of putrescine, spermidine and spermine, and increased the PAs contents, indicating higher metabolic gene expression. Moreover, melatonin-pretreated seedlings had further increased PAs levels and upregulated transcript abundance, which coincided with suppression of catabolic-related genes expression. Under heat stress, exogenous melatonin increased endogenous NO content along with nitrate reductase- and NO synthase-related activities, and expression of their related genes were also elevated.ConclusionsMelatonin pretreatment positively increased the heat tolerance of tomato seedlings by improving their antioxidant defense mechanism, inducing ascorbate-glutathione cycle, and reprogramming the PAs metabolic and NO biosynthesis pathways. These attributes facilitated the scavenging of excess ROS and increased stability of the cellular membrane, which mitigated heat-induced oxidative stress.

Dataset Information

VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC.

Publications

VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC.

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