Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen

Xu, Yajie; Qiang, Min; Zhang, Jinling; Liu, Ying; He, Rong

doi:10.1007/s13238-012-2057-y

Cited by 21 publications

(13 citation statements)

References 52 publications

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“…Means of formaldehyde concentrations or blot den-sities among groups were compared by ANOVA followed by a post-hoc test. Statistical analyses were performed with Origin 5.0 and SPSS 16.0 [63].…”

Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

Lü

Zhou

et al. 2013

JAD

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Hyperphosphorylation of tau occurs in preclinical and clinical stages of Alzheimer's disease (AD), and hyperphosphorylated tau is the main constituent of the paired helical filaments in the brains of mild cognitive impairment and AD patients. While most of the work described so far focused on the relationship between hyperphosphorylation of tau and microtubule disassembly as well as axonal transport impairments, both phenomena ultimately leading to cell death, little work has been done to study the correlation between tau hyperphosphorylation and DNA damage. As we showed in this study, tau hyperphosphorylation and DNA damage co-occurred under formaldehyde treatment in N2a cells, indicating that phosphorylated tau (p-Tau) induced by formaldehyde may be involved in DNA impairment. After phosphorylation, the effect of tau in preventing DNA from thermal denaturation was diminished, its ability to accelerate DNA renaturation was lost, and its function in protecting DNA from reactive oxygen species (ROS) attack was impaired. Thus, p-Tau is not only associated with the disassembly of the microtubule system, but also plays a crucial role in DNA impairment. Hyperphosphorylation-mediated dysfunction of tau protein in prevention of DNA structure from damage under the attack of ROS may provide novel insights into the mechanisms underlying tauopathies.

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Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

Lü

Zhou

et al. 2013

JAD

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“…In addition to that, reactive carbonyl compounds seem to also contribute to aggregation and dysfunction of fibrinogen. Its deposition on blood vessel walls plays an important role in the pathology of atherosclerosis as well [207]. …”

Section: Carbonyl Stress and Copdmentioning

confidence: 99%

The Role of Mitochondria and Oxidative/Antioxidative Imbalance in Pathobiology of Chronic Obstructive Pulmonary Disease

Białas

Sitarek

Miłkowska-Dymanowska

et al. 2016

Oxidative Medicine and Cellular Longevity

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Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. The major risk factor of COPD, which has been proven in many studies, is the exposure to cigarette smoke. However, it is 15–20% of all smokers who develop COPD. This is why we should recognize the pathobiology of COPD as involving a complex interaction between several factors, including genetic vulnerability. Oxidant-antioxidant imbalance is recognized as one of the significant factors in COPD pathogenesis. Numerous exogenous and endogenous sources of ROS are present in pathobiology of COPD. One of endogenous sources of ROS is mitochondria. Although leakage of electrons from electron transport chain and forming of ROS are the effect of physiological functioning of mitochondria, there are various intra- and extracellular factors which may increase this amount and significantly contribute to oxidative-antioxidative imbalance. With the coexistence with impaired antioxidant defence, all these issues lead to oxidative and carbonyl stress. Both of these states play a significant role in pathobiology of COPD and may account for development of major comorbidities of this disease.

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“…The extent of these changes depends on the nature of reagents and the length of fibrinogen exposure to reagents [33,39]. Reports have revealed that fibrinogen oxidation [35], nitration [4], and its reaction with reactive carbonyl compounds [40] do not change its secondary structure within the detection limit of circular dichroism.…”

Section: Introductionmentioning

confidence: 99%

Impact of posttranslational modifications on atomistic structure of fibrinogen

et al. 2020

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Oxidative stress in humans is related to various pathophysiological processes, which can manifest in numerous diseases including cancer, cardiovascular diseases, and Alzheimer's disease. On the atomistic level, oxidative stress causes posttranslational modifications, thus inducing structural and functional changes into the proteins structure. This study focuses on fibrinogen, a blood plasma protein that is frequently targeted by reagents causing posttranslational modifications in proteins. Fibrinogen was in vitro modified by three reagents, namely sodium hypochlorite, malondialdehyde, and 3-morpholinosydnonimine that mimic the oxidative stress in diseases. Newly induced posttranslational modifications were detected via mass spectrometry. Electron microscopy was used to visualize changes in the fibrin networks, which highlight the extent of disturbances in fibrinogen behavior after exposure to reagents. We used molecular dynamics simulations to observe the impact of selected posttranslational modifications on the fibrinogen structure at the atomistic level. In total, 154 posttranslational modifications were identified, 84 of them were in fibrinogen treated with hypochlorite, 51 resulted from a reaction of fibrinogen with malondialdehyde, and 19 were caused by 3-morpholinosydnonimine. Our data reveal that the stronger reagents induce more posttranslational modifications in the fibrinogen structure than the weaker ones, and they extensively alter the architecture of the fibrin network. Molecular dynamics simulations revealed that the effect of posttranslational modifications on fibrinogen secondary structure varies from negligible alternations to serious disruptions. Among the serious disruptions is the oxidation of γR375 resulting in the release of Ca 2+ ion that is necessary for appropriate fibrin fiber formation. Folding of amino acids γE72-γN77 into a short α-helix is a result of oxidation of γP76 to glutamic acid. The study describes behaviour of fibrinogen coiled-coil connecter in the vicinity of plasmin and hementin cleavage sites.

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Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen

Cited by 21 publications

References 52 publications

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

The Role of Mitochondria and Oxidative/Antioxidative Imbalance in Pathobiology of Chronic Obstructive Pulmonary Disease

Impact of posttranslational modifications on atomistic structure of fibrinogen

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