Restoration of Polyamine Metabolic Patterns in <i>In Vivo</i> and <i>In Vitro</i> Model of Ischemic Stroke following Human Mesenchymal Stem Cell Treatment

Shin, Tae Hwan; Phukan, Geetika; Shim, Jeom Soon; Nguyen, Duc-Toan; Kim, Yongman; Oh-Lee, Justin Do-hoon; Lee, Hyeon‐Seong; Paik, Man‐Jeong; Lee, Gwang

doi:10.1155/2016/4612531

Cited by 21 publications

(23 citation statements)

References 44 publications

(56 reference statements)

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“…These approaches facilitate the identification of new biomarkers and biological functions and can aid in the understanding of physiologic and pathologic states. The event of cerebral ischemia likely triggers a multifaceted cascade of metabolic and biochemical events through metabolic changes caused by brain damage as detected in clinical samples and animal models [13,14,65]. These findings accentuate the need for advanced bioinformatic cellular metabolic analyses.…”

Section: Metabolite Analytical Methods and Data Interpretation Platfomentioning

confidence: 99%

Metabolome Changes in Cerebral Ischemia

Shin

Lee

Basith

et al. 2020

Cells

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103

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Cerebral ischemia is caused by perturbations in blood flow to the brain that trigger sequential and complex metabolic and cellular pathologies. This leads to brain tissue damage, including neuronal cell death and cerebral infarction, manifesting clinically as ischemic stroke, which is the cause of considerable morbidity and mortality worldwide. To analyze the underlying biological mechanisms and identify potential biomarkers of ischemic stroke, various in vitro and in vivo experimental models have been established investigating different molecular aspects, such as genes, microRNAs, and proteins. Yet, the metabolic and cellular pathologies of ischemic brain injury remain not fully elucidated, and the relationships among various pathological mechanisms are difficult to establish due to the heterogeneity and complexity of the disease. Metabolome-based techniques can provide clues about the cellular pathologic status of a condition as metabolic disturbances can represent an endpoint in biological phenomena. A number of investigations have analyzed metabolic changes in samples from cerebral ischemia patients and from various in vivo and in vitro models. We previously analyzed levels of amino acids and organic acids, as well as polyamine distribution in an in vivo rat model, and identified relationships between metabolic changes and cellular functions through bioinformatics tools. This review focuses on the metabolic and cellular changes in cerebral ischemia that offer a deeper understanding of the pathology underlying ischemic strokes and contribute to the development of new diagnostic and therapeutic approaches.

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Section: Metabolite Analytical Methods and Data Interpretation Platfomentioning

confidence: 99%

Metabolome Changes in Cerebral Ischemia

Shin

Lee

Basith

et al. 2020

Cells

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103

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“…In ischemic stroke, spermine significantly reduces infarction and neurological deficit [ 90 ]. Human mesenchymal stem cell treatment has a limited ability to restore cellular polyamine homeostasis, while levels of its metabolic products putrescine and spermidine significantly increase [ 91 ]. After CNS injuries such as ischemia and trauma, energy failure causing intracellular signaling disruption and several deleterious cascades are activated resulting in axonal degeneration and neuron death [ 92 , 93 ].…”

Section: Mechanisms Of Stem Cell Transplantation To Treat Ischemicmentioning

confidence: 99%

Potential Therapeutic Mechanisms and Tracking of Transplanted Stem Cells: Implications for Stroke Treatment

Zhang

Yao

2017

Stem Cells International

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Stem cell therapy is a promising potential therapeutic strategy to treat cerebral ischemia in preclinical and clinical trials. Currently proposed treatments for stroke employing stem cells include the replacement of lost neurons and integration into the existing host circuitry, the release of growth factors to support and promote endogenous repair processes, and the secretion of extracellular vesicles containing proteins, noncoding RNA, or DNA to regulate gene expression in recipient cells and achieve immunomodulation. Progress has been made to elucidate the precise mechanisms underlying stem cell therapy and the homing, migration, distribution, and differentiation of transplanted stem cells in vivo using various imaging modalities. Noninvasive and safe tracer agents with high sensitivity and image resolution must be combined with long-term monitoring using imaging technology to determine the optimal therapy for stroke in terms of administration route, dosage, and timing. This review discusses potential therapeutic mechanisms of stem cell transplantation for the treatment of stroke and the limitations of current therapies. Methods to label transplanted cells and existing imaging systems for stem cell labeling and in vivo tracking will also be discussed.

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“…In the present research, we used a well characterized human SH-SY5Y neuroblastoma cell line which has been previously utilized in studies characterizing neurological disorders (Petratos et al, 2008; Wu et al, 2014), Mn (Maddirala et al, 2015; Zhang et al, 2016) and polyamine metabolism (Phukan et al, 2016; Shin et al, 2016). The possible link between Mn and polyamine metabolism and its implications in neurological disorders however, are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells

Fernandes

Chandler

Liu

et al. 2018

Food and Chemical Toxicology

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Disrupted polyamine metabolism with elevated putrescine is associated with neuronal dysfunction. Manganese (Mn) is an essential nutrient that causes neurotoxicity in excess, but methods to evaluate biochemical responses to high Mn are limited. No information is available on dose-response effects of Mn on putrescine abundance and related polyamine metabolism. The present research was to test the hypothesis that Mn causes putrescine accumulation over a physiologically adequate to toxic concentration range in a neuronal cell line. We used human SH-SY5Y neuroblastoma cells treated with MnCl2 under conditions that resulted in cell death or no cell death after 48 h. Putrescine and other metabolites were analyzed by liquid chromatography-ultra high-resolution mass spectrometry. Putrescine-related pathway changes were identified with metabolome-wide association study (MWAS). Results show that Mn caused a dose-dependent increase in putrescine over a non-toxic to toxic concentration range. MWAS of putrescine showed positive correlations with the polyamine metabolite N8-acetylspermidine, methionine-related precursors, and arginine-associated urea cycle metabolites, while putrescine was negatively correlated with γ-aminobutyric acid (GABA)-related and succinate-related metabolites (P < 0.001, FDR < 0.01). These data suggest that measurement of putrescine and correlated metabolites may be useful to study effects of Mn intake in the high adequate to UL range.

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Restoration of Polyamine Metabolic Patterns in In Vivo and In Vitro Model of Ischemic Stroke following Human Mesenchymal Stem Cell Treatment

Cited by 21 publications

References 44 publications

Metabolome Changes in Cerebral Ischemia

Metabolome Changes in Cerebral Ischemia

Potential Therapeutic Mechanisms and Tracking of Transplanted Stem Cells: Implications for Stroke Treatment

Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells

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