Integrating proteomic, lipidomic and metabolomic data to construct a global metabolic network of lethal ventricular tachyarrhythmias (LVTA) induced by aconitine

Xie, Dezhi; Wu, Jiayan; Wu, Qian; Zhang, Xiaojun; Zhou, Danya; Dai, Wentao; Zhu, Mengting; Wang, Dian

doi:10.1016/j.jprot.2020.104043

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…The results demonstrated upregulation of approximately 250 proteins and downregulation of approximately 200 other proteins in the LVTA group, suggesting an important disturbance in protein expression during the arrhythmogenic process. Investigations demonstrated important changes in proteins involved in energy metabolism, such as beta oxidation of fatty acids and tricarboxylic acid, inactivation of protein kinase C and NAPDH, alterations of the oxidase pathway, and alterations in proteins involved in intracellular calcium homeostasis, with increased oxidative stress and decreased ATP production [ 48 ]. In a similar study, the authors again, using an animal protocol with rats, induced LVTA by ligation of the coronary artery.…”

Section: Resultsmentioning

confidence: 99%

Exploring the Potential of Proteome Analysis as a Promising Tool for Evaluation of Sudden Cardiac Death (SCD) in Forensic Settings: A Literature Review

Sacco,

Gualtieri,

Calanna

et al. 2023

IJMS

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Sudden cardiac death (SCD) represents a global emergency, with a high number of cases affecting all age groups every year. The prevention of these fatal events requires an accurate knowledge of etiology and pathogenesis, which can vary. Autopsy is an indispensable tool in cases of SCD for diagnostic purposes, as well as for judicial and preventive purposes for family members. Despite the completion of all routine post-mortem investigations, it is often complicated for the forensic pathologist to define the triggering cause of these events. The study of the proteome is proving to be extremely promising in the field of human cardiovascular disease. This paper aims to offer a literature review on the study of the proteome in post-mortem cadaveric biological samples obtained from SCD cases. The aim of this work is to outline the state of the art of the scientific advances that protein analysis can offer in the diagnosis of SCD and the limits that various studies have traced up to now. In conclusion, the work defines the future perspectives of this field in SCD, suggesting strategies to overcome the reported limits and improve the diagnostics of these events.

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Section: Resultsmentioning

confidence: 99%

Exploring the Potential of Proteome Analysis as a Promising Tool for Evaluation of Sudden Cardiac Death (SCD) in Forensic Settings: A Literature Review

Sacco,

Gualtieri,

Calanna

et al. 2023

IJMS

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Section: Methodsmentioning

confidence: 99%

“…The phosphoproteome was analyzed according to previous studies ( 18 , 19 ). A total of 1 mg protein from each left ventricular myocardium was treated with the filter-aided sample preparation (FASP) method ( 18 ), followed by digestion with trypsin (1:50, w/w; Promega Corporation) overnight at 37°C. The peptides were then dried by vacuum centrifugation (1,000 g, −25°C, 3 h), followed by phosphorylated peptide enrichment using the High-Select™ TiO 2 Phosphopeptide Enrichment kit (Thermo Fisher Scientific, Inc.), according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

mROS‑calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia

Zhou,

Zhang,

Zhu

et al. 2023

Int J Mol Med

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Lethal ventricular arrhythmia-sudden cardiac death (LVA-SCD) occurs frequently during the early stage of myocardial ischemia (MI). However, the mechanism underlying higher LVA-SCD incidence is still poorly understood. The present study aimed to explore the role of mitochondrial reactive oxygen species (mROS) and Ca 2+ crosstalk in promoting LVA-SCD in early MI. RyR2 S2814A mice and their wild-type littermates were used. MitoTEMPO was applied to scavenge mitochondrial ROS (mROS). Mice were subjected to severe MI and the occurrence of LVA-SCD was evaluated. Levels of mitochondrial ROS and calcium (mitoCa 2+ ), cytosolic ROS (cytoROS), and calcium (cytoCa 2+ ), RyR2 Ser-2814 phosphorylation, CaMKII Met-282 oxidation, mitochondrial membrane potential (MMP), and glutathione/oxidized glutathione (GSH/GSSG) ratio in the myocardia were detected. Dynamic changes in mROS after hypoxia were investigated using H9c2 cells. Moreover, the myocardial phosphoproteome was analyzed to explore the related mechanisms facilitating mROS-Ca 2+ crosstalk and LVA-SCD. There was a high incidence (~33.9%) of LVA-SCD in early MI. Mice who underwent SCD displayed notably elevated levels of myocardial ROS and mROS, and the latter was validated in H9c2 cells. These mice also demonstrated overloads of cytoplasmic and mitochondrial Ca 2+ , decreased MMP and reduced GSH/GSSG ratio, upregulated RyR2-S2814 phosphorylation and CaMKII-M282 oxidation and transient hyperphosphorylation of mitochondrial proteomes in the myocardium. mROS-specific scavenging by a mitochondria-targeted antioxidant agent (MitoTEMPO) corrected these SCD-induced alterations. S2814A mice with a genetically inactivated CaMKII phosphorylation site in RyR2 exhibited decreased overloads in cytoplasmic and mitochondrial Ca 2+ and demonstrated similar effects as MitoTEMPO to correct SCD-induced changes and prevent SCD post-MI. The data confirmed crosstalk between mROS and Ca 2+ in promoting LVA-SCD. Therefore, we provided evidence that there is a higher incidence of LVA-SCD in early MI, which may be attributed to a positive feedback loop between mROS and Ca 2+ imbalance.

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“…The AGC target was set as 3e6 with a maximum injection time of 200 ms. Top 20 multiply charged precursor ions were selected for collision induced dissociation (CID) analysis in the linear ion trap with centroid data type. Activation times were 30 ms for CID fragmentation with normalized collision energy of 35.0 [11].…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

Serum proteomics reveals the proteomic characteristics involved in the progressive feature of acute ischemic stroke (AIS)

Lai

Zhang

Zhou

et al. 2021

Preprint

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Background To distinguish acute progressive ischemic stroke (APIS) from acute non-progressive ischemic stroke (ANPIS) is clinically critical for the precise treatment and prevention of acute ischemic stroke (AIS) deterioration. Serum proteins could reflect the unique pathophysiological processes of APIS. It is expected to find serum protein biomarkers to identify APIS at the early state, especially when typical symptoms have not been present in conventional clinical indices. Methods We recruited 178 subjects, including 133 AIS patients and 45 healthy controls. The discovery set, which included 10 age- and sex- matched cases from each of the APIS, ANPIS and control groups, was used for serum proteomic analysis with a mass spectrometry-based proteomics. The disrupted proteins of APIS were screened, of which, those common to ANPIS and specific to APIS were particularly concerned. Potential biomarkers of APIS were screened based on the theoretical knowledge to explain the mechanism and diagnostic value, and subsequently tested in the validated set (25 APIS patients, 88 ANPIS patients, and 35 controls). Results We found that 46 serum proteins were disturbed in the APIS patients; 23 differentially expressed proteins (DEPs) were common to these two groups, and 23 DEPs were associated with APIS alone. Enrichment analysis suggested that complement activation, cytolysis, proteolysis, positive regulation of fibrinolysis, blood coagulation were specifically associated with APIS; while inflammatory response, neutrophil chemotaxis, oxygen transport, and positive regulation of cell death process were common to AIPS and ANPIS. Serum amyloid A1 (SAA1) and S100 calcium binding protein A9 (S100-A9) jointly conferred a moderate value (AUC = 0.799) to diagnose APIS and to distinguish APIS from ANPIS (AUC = 0.699). Conclusions This study provides human serum proteomic evidence that inflammation, oxidative stress, and necrosis in APIS are common to ANPIS; the progressive feature of APIS may be mainly associated with complement activation, more serious inflammation, and lipid metabolic disorder; SAA1 and S100-A9 may be considered as potential biomarker panel of APIS.

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Integrating proteomic, lipidomic and metabolomic data to construct a global metabolic network of lethal ventricular tachyarrhythmias (LVTA) induced by aconitine

Cited by 8 publications

References 40 publications

Exploring the Potential of Proteome Analysis as a Promising Tool for Evaluation of Sudden Cardiac Death (SCD) in Forensic Settings: A Literature Review

Exploring the Potential of Proteome Analysis as a Promising Tool for Evaluation of Sudden Cardiac Death (SCD) in Forensic Settings: A Literature Review

mROS‑calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia

Serum proteomics reveals the proteomic characteristics involved in the progressive feature of acute ischemic stroke (AIS)

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