Multi-omics analyses of red blood cell reveal antioxidation mechanisms associated with hemolytic toxicity of gossypol

Tang, Chaohua; Meng, Qingshi; Zhang, Kai; Zhan, Tengfei; Zhao, Qingyu; Zhang, Sheng; Zhang, Junmin

doi:10.18632/oncotarget.21779

Cited by 9 publications

(6 citation statements)

References 35 publications

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“…164 This compound also induces an accelerated hemolytic toxicity when administered in vivo. 165 The interference with RBPs represents an additional perspective that contributes to defining the broad mechanism of action of gossypol and its preferential intracellular targets at the tissue-specific level.…”

Section: Musashimentioning

confidence: 99%

Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery

et al. 2019

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RNA-binding proteins (RBPs) are pleiotropic factors that control the processing and functional compartmentalization of transcripts by binding primarily to mRNA untranslated regions (UTRs). The competitive and/or cooperative interplay between RBPs and an array of coding and noncoding RNAs (ncRNAs) determines the posttranscriptional control of gene expression, influencing protein production. Recently, a variety of well-recognized and noncanonical RBP domains have been revealed by modern system-wide analyses, underlying an evolving classification of ribonucleoproteins (RNPs) and their importance in governing physiological RNA metabolism. The possibility of targeting selected RNA–protein interactions with small molecules is now expanding the concept of protein “druggability,” with new implications for medicinal chemistry and for a deeper characterization of the mechanism of action of bioactive compounds. Here, taking SF3B1, HuR, LIN28, and Musashi proteins as paradigmatic case studies, we review the strategies applied for targeting RBPs, with emphasis on the technological advancements to study protein–RNA interactions and on the requirements of appropriate validation strategies to parallel high-throughput screening (HTS) efforts.

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Section: Musashimentioning

confidence: 99%

Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery

et al. 2019

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“…This enzyme contains in the cytoplasm of cells in the form of a tripeptide -glycine-cysteine-glutamic acid. Cysteine SH-groups are extremely sensitive to the peroxides action [28,29]. Consequently, it is clear that an increase in GR indicates the active involvement of glutathione in reducing cellular damage by free radicals in various pathologies, including TBI [25].…”

Section: Discussionmentioning

confidence: 99%

The state of antioxidant system and emotional status in rats with mild blast-induced traumatic brain injury

Kozlova,

Maslak,

Netronina

et al. 2024

Zaporozhye Medical Journal

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The aim was to evaluate the markers of emotional status and the antioxidant system activity in rats with blast-induced traumatic brain injury. Materials and methods. The study carried out on 85 sexually mature male Wistar rats in compliance with the current legislation on humane treatment of animals. The selected rats were randomly divided into three groups: I – study in the Barnes maze; II – study in the Open Field test; and III – study of glutathione reductase activity in a solution of rat erythrocyte’s hemolysate. In each of these groups, three groups were formed: Experimental – exposed to a shock wave with an overpressure of 26.4 ± 3.6 kPa; the Sham – subjected only to halothane and fixation; and the Intact group. Results. Showed a disturbance in the emotional status and the oxidative stress development in rats with blast-induced trauma. The time of experimental rats freezing in the Barnes maze increased by 69 % (p < 0.01) on 28th day compared to 1st day, indicating the development of fear and negative emotionality. Changes in the defecation acts number indicate the development of anxiety in the acute period (1–3 days), followed by a depression-like state. The glutathione reductase activity in experimental rats was significantly higher compared to sham and intact rats, but gradually decreased inside in the experimental group. The results of the correlation analysis indicate the presence of weak relationships between the freezing time and the glutathione reductase activity. The positive relationship of a strong degree was found between the number of defecation acts and glutathione reductase on 1st day and a negative relationship of a strong degree was found on 7th day. Conclusions. We suppose that oxidative stress is a link, but not the leading one, in the pathogenesis of emotional disturbance in rats with blast-induced brain injury.

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“…The development of omics technologies and increased generation of high-throughput omics data have inevitably called for powerful systematic means to analyze them in an integrated manner. Omics, a new way for exploring the pathogenesis of human diseases, is categorized into genomics, epigenomics, transcriptomics, and proteomics, and multiple authors have reported about RBCs and OMICs integrations [ 225 , 226 , 227 , 228 ].…”

Section: Extracellular Vesicles Cargomentioning

confidence: 99%

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

Sanz-Rubio

2021

IJMS

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Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).

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Multi-omics analyses of red blood cell reveal antioxidation mechanisms associated with hemolytic toxicity of gossypol

Cited by 9 publications

References 35 publications

Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery

Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery

The state of antioxidant system and emotional status in rats with mild blast-induced traumatic brain injury

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

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