Extracellular superoxide dismutase is present in secretory vesicles of human neutrophils and released upon stimulation

Iversen, Marie B.; Gottfredsen, Randi H.; Larsen, Ulrike G.; Enghild, Jan J.; Prætorius, Jeppe; Borregaard, Niels; Petersen, Steen V.

doi:10.1016/j.freeradbiomed.2016.07.004

Cited by 32 publications

(25 citation statements)

References 55 publications

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“…The enzyme is known to associate with macrophages and PMNs, and increasing evidence supports a role for EC-SOD in the development of inflammatory responses. Moreover, Iversen et al (2016) reported that human EC-SOD is present at the cell surface of isolated neutrophils as well as stored within secretory vesicles. As EC-SOD is associated with neutrophil extracellular traps (NETs) along with MPO and reduces the levels of extracellular superoxide, it is plausible that the enzymatic activity of EC-SOD provides H 2 O 2 to MPO based on O 2 − generated by Nox.…”

mentioning

confidence: 99%

Independent trafficking of flavocytochrome b558 and myeloperoxidase to phagosomes during phagocytosis visualised by energy‐filtering and energy‐dispersive spectroscopy‐scanning transmission electron microscopy

Moriguchi

2017

Journal of Microscopy

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When polymorphonuclear leukocytes (PMNs) phagocytose opsonised zymosan particles (OPZ), free radicals and reactive oxygen species (ROS) are formed in the phagosomes. ROS production is mediated by NADPH oxidase (Nox), which transfers electrons in converting oxygen to superoxide (O ). Nox-generated O is rapidly converted to other ROS. Free radical-forming secretory vesicles containing the Nox redox center flavocytochrome b558, a membrane protein, and azurophil granules with packaged myeloperoxidase (MPO) have been described. Presuming the probable fusion of these vesicular and granular organelles with phagosomes, the translation process of the enzymes was investigated using energy-filtering and energy-dispersive spectroscopy-scanning transmission electron microscopy. In this work, the primary method for imaging cerium (Ce) ions demonstrated the localisation of H O generated by phagocytosing PMNs. The MPO activity of the same PMNs was continuously monitored using 0.1% 3,3'-diaminobenzidine-tetrahydrochloride (DAB) and 0.01% H O . A detailed view of these vesicular and granular structures was created by overlaying each electron micrograph with pseudocolors: blue for Ce and green for nitrogen (N).

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mentioning

confidence: 99%

Independent trafficking of flavocytochrome b558 and myeloperoxidase to phagosomes during phagocytosis visualised by energy‐filtering and energy‐dispersive spectroscopy‐scanning transmission electron microscopy

Moriguchi

2017

Journal of Microscopy

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“…Histological evaluation of H&E slides showed no differences in neutrophil invasion into the myocardium particularly in POPs treated groups. While prior studies have used neutrophil population as a predictor for changes in SOD levels, our findings suggest changes in neutrophil numbers may have either occurred early in POPs exposure timeframe or depleted over time with chronic exposure culminating in decreased SOD levels . Future studies will be performed using known positive control agents, such as doxorubicin.…”

Section: Discussionmentioning

confidence: 79%

Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling

Coole

Burr

Kay

et al. 2019

Environmental Toxicology

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Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end‐product (AGE)‐and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5‐weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6‐weeks. At the end of 6‐weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE‐RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α‐smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase‐1 and ‐2 (SOD‐1 and SOD‐2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling.

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“…It has been suggested that ecSOD can be stored in intracellular vesicles in tissues which have the potential to be secreted upon stimulation [29] [30] [31] [32]. Previous study, which has shown localization of ecSOD in the endosomal fraction [33], suggests that there might be some degradation of intracellular ecSOD.…”

Section: Discussionmentioning

confidence: 99%

Allele-Specific Effects on Extracellular Superoxide Dismutase Synthesis and Secretion

Jun¹,

Dory²

2017

JBiSE

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Plasma extracellular superoxide dismutase (ecSOD) concentrations are significantly (2 -3-fold) higher in 129 mice than in the C57 strain. We reported earlier that the 129 strain carries a different allele of this enzyme, characterized by two amino acid substitutions and a 10 bp deletion in the 3'UTR of the mRNA. One of the substitutions is at the signal peptide cleavage site (position 21) while the other is within the catalytic site. Since the differences in plasma enzyme concentrations persist in congenic mice expressing the different alleles, the differences in plasma concentrations appear to be largely allele-driven and independent of the remainder of the genome. As expected, in vitro translation using rabbit reticulocyte lysate showed no differences in translational efficiency of transcripts and processing of the newly synthesized enzymes. Determinations of the rates of synthesis and secretion of the two isoforms of this enzyme in stably transfected CHO cells clearly demonstrate that the mature 129 variant is synthesized at rates nearly twice those of the wild-type isoform and has an intracellular pool size twice as large. However, both isoforms are secreted at the same fractional rate and have identical intracellular T 1/2 as well as similar extent of degradation. These data explain, at least partially, the higher levels of ecSOD in congenic mice expressing the 129 variant, as well as enzyme levels in the 129 strain of mice. In silico calculations support this conclusion and indicate that the aa change at the signal peptide cleavage site (N21D) results in a substantial increase in cleavage probability at this site for the 129 variant. Our results also highlight the importance of signal peptide cleavage in determining steady-state levels of secretory proteins.

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Extracellular superoxide dismutase is present in secretory vesicles of human neutrophils and released upon stimulation

Cited by 32 publications

References 55 publications

Independent trafficking of flavocytochrome b558 and myeloperoxidase to phagosomes during phagocytosis visualised by energy‐filtering and energy‐dispersive spectroscopy‐scanning transmission electron microscopy

Independent trafficking of flavocytochrome b558 and myeloperoxidase to phagosomes during phagocytosis visualised by energy‐filtering and energy‐dispersive spectroscopy‐scanning transmission electron microscopy

Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling

Allele-Specific Effects on Extracellular Superoxide Dismutase Synthesis and Secretion

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