Hypochlorite-induced aggregation of fibrinogen underlies a novel antioxidant role in blood plasma

Mañucat-Tan, Noralyn B.; Abdallah, Rafaa Zeineddine; Harsimran, Kaur; Saviane, Daniel; Wilson, Mark R.; Wyatt, Amy R.

doi:10.1016/j.redox.2020.101847

Cited by 11 publications

(6 citation statements)

References 87 publications

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“…Many relevant studies have used metal-catalysed systems to study the effect of oxidation on Aβ, yet hydroxyl radicals ( • OH; produced by metal-catalysed Fenton chemistry) are just one of many biological oxidants that are generated during inflammation. A growing body of work has demonstrated that the functional consequences of protein oxidation are dependent on both the oxidant and the protein identity [ [15] , [16] , [17] , [18] ], as such there is a need to assess the specific effects of individual biological oxidants on the functions of Aβ.…”

Section: Introductionmentioning

confidence: 99%

Hypochlorite-induced oxidation promotes aggregation and reduces toxicity of amyloid beta 1-42

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Hypochlorite-induced oxidation promotes aggregation and reduces toxicity of amyloid beta 1-42

et al. 2023

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“…Cellular free radicals and the circadian clock are interconnected; thus, alterations in antioxidants’ defence mechanisms result in fish circadian disruption (Zheng et al 2021 ). NaOCl has the potential to cross-link fibrinogen and affect blood plasma antioxidants defence mechanisms (immunostimulatory properties) (Manucat-Tan et al 2021 ). Bao et al ( 2019 ) reported that waterborne contaminants (perfluorooctane sulfonate) affect networking genes (hypothalamus-pituitary–gonadal-liver axis) of female zebrafish.…”

Section: Discussionmentioning

confidence: 99%

Assessment of eco-toxic effects of commonly used water disinfectant on zebrafish (Danio rerio) swimming behaviour and recovery responses: an early-warning biomarker approach

Ren

Ramesh

et al. 2022

Environ Sci Pollut Res

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Eco-toxicity profiles for commonly used disinfectants were lacking. Available traditional toxicity techniques have some limitations (assessments and ethical issues). Behaviour toxicology is a promising research area towards early warning and non-invasive approaches. We studied the potential eco-toxic effects of sodium hypochlorite (NaOCl) on the swimming behaviour of zebrafish. Zebrafish were exposed to different concentrations (Treatment I, Treatment II, Treatment III, and Treatment IV) of NaOCl for 360 h. Recovery study (144 h) was conducted for NaOCl treatment groups. The swimming behaviour of zebrafish was quantified efficiently using an online monitoring system (OMS). OMS dataset was processed for determination of behavioural differences by MATLAB and SPSS. Compared to the control group, the swimming strength of zebrafish under NaOCl treatments declined significantly ( p < 0.001). Avoidance behaviour has occurred on zebrafish under NaOCl exposure periods. Furthermore, NaOCl toxicity also adjusted circadian rhythms on zebrafish. Zebrafish swimming strength was significantly ( p < 0.001) improved under-recovery periods. Moreover, normal diurnal patterns have occurred. NaOCl could cause behavioural abnormalities in non-target organisms. Continuous exposure to common disinfectants could cause external and internal stress on non-target organisms, resulting in behavioural changes and circadian rhythm adjustments. Continuous changes in behavioural and circadian rhythms might reduce organisms’ fitness and adaptation capacity. This study highlights (1) the importance of computer-based toxicity assessments, and (2) swimming behaviour is an early warning biomarker for eco-toxicity studies. Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-18333-1.

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“…In conclusion, this study forms part of a growing body of work characterising how the proteome is exquisitely responsive to hypochlorite-induced oxidative stress [ 42 , 62 , 63 ]. A more detailed understanding of molecular adaptations to oxidative stress could help to reveal novel therapeutic strategies for controlling proteostasis in a broad range of inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

A Novel Role for Plasminogen Activator Inhibitor Type-2 as a Hypochlorite-Resistant Serine Protease Inhibitor and Holdase Chaperone

Cater

Mañucat-Tan

Georgiou

et al. 2022

Cells

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Plasminogen activator inhibitor type-2 (PAI-2), a member of the serpin family, is dramatically upregulated during pregnancy and in response to inflammation. Although PAI-2 exists in glycosylated and non-glycosylated forms in vivo, the majority of in vitro studies of PAI-2 have exclusively involved the intracellular non-glycosylated form. This study shows that exposure to inflammation-associated hypochlorite induces the oligomerisation of PAI-2 via a mechanism involving dityrosine formation. Compared to plasminogen activator inhibitor type-1 (PAI-1), both forms of PAI-2 are more resistant to hypochlorite-induced inactivation of its protease inhibitory activity. Holdase-type extracellular chaperone activity plays a putative non-canonical role for PAI-2. Our data demonstrate that glycosylated PAI-2 more efficiently inhibits the aggregation of Alzheimer’s disease and preeclampsia-associated amyloid beta peptide (Aβ), compared to non-glycosylated PAI-2 in vitro. However, hypochlorite-induced modification of non-glycosylated PAI-2 dramatically enhances its holdase activity by promoting the formation of very high-molecular-mass chaperone-active PAI-2 oligomers. Both PAI-2 forms protect against Aβ-induced cytotoxicity in the SH-SY5Y neuroblastoma cell line in vitro. In the villous placenta, PAI-2 is localised primarily to syncytiotrophoblast with wide interpersonal variation in women with preeclampsia and in gestational-age-matched controls. Although intracellular PAI-2 and Aβ staining localised to different placental cell types, some PAI-2 co-localised with Aβ in the extracellular plaque-like aggregated deposits abundant in preeclamptic placenta. Thus, PAI-2 potentially contributes to controlling aberrant fibrinolysis and the accumulation of misfolded proteins in states characterised by oxidative and proteostasis stress, such as in Alzheimer’s disease and preeclampsia.

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Hypochlorite-induced aggregation of fibrinogen underlies a novel antioxidant role in blood plasma

Cited by 11 publications

References 87 publications

Hypochlorite-induced oxidation promotes aggregation and reduces toxicity of amyloid beta 1-42

Hypochlorite-induced oxidation promotes aggregation and reduces toxicity of amyloid beta 1-42

Assessment of eco-toxic effects of commonly used water disinfectant on zebrafish (Danio rerio) swimming behaviour and recovery responses: an early-warning biomarker approach

A Novel Role for Plasminogen Activator Inhibitor Type-2 as a Hypochlorite-Resistant Serine Protease Inhibitor and Holdase Chaperone

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