Regulation of cardiac O-GlcNAcylation: More than just nutrient availability

Collins, Helen E.; Chatham, John C.

doi:10.1016/j.bbadis.2020.165712

Cited by 22 publications

(16 citation statements)

References 114 publications

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“…O-GlcNAcylation is a post-translational modification analogous to phosphorylation that is regulated by nutrient availability and cellular stress [140][141][142] O-linked Nacetylglucosamine (O-GlcNAc) is a product of the hexosamine biosynthetic pathway that attaches to serine and threonine protein residues by O-GlcNAc transferase (OGT) and can be removed by O-GlcNAcase (OGA) [140]. Dysregulation of O-GlcNAc glycosylation adversely affects mitochondrial function [143].…”

Section: O-glcnacylationmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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Current methods to differentiate cardiomyocytes from human pluripotent stem cells (PSCs) inadequately recapitulate complete development and result in PSC-derived cardiomyocytes (PSC-CMs) with an immature or fetal-like phenotype. Embryonic and fetal development are highly dynamic periods during which the developing embryo or fetus is exposed to changing nutrient, oxygen, and hormone levels until birth. It is becoming increasingly apparent that these metabolic changes initiate developmental processes to mature cardiomyocytes. Mitochondria are central to these changes, responding to these metabolic changes and transitioning from small, fragmented mitochondria to large organelles capable of producing enough ATP to support the contractile function of the heart. These changes in mitochondria may not simply be a response to cardiomyocyte maturation; the metabolic signals that occur throughout development may actually be central to the maturation process in cardiomyocytes. Here, we review methods to enhance maturation of PSC-CMs and highlight evidence from development indicating the key roles that mitochondria play during cardiomyocyte maturation. We evaluate metabolic transitions that occur during development and how these affect molecular nutrient sensors, discuss how regulation of nutrient sensing pathways affect mitochondrial dynamics and function, and explore how changes in mitochondrial function can affect metabolite production, the cell cycle, and epigenetics to influence maturation of cardiomyocytes.

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Section: O-glcnacylationmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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“…O -GlcNAcylation, a nutrient-driven post-translational modifications in nucleoplasmic protein, has been newly identified as an endogenous prosurvival pathway, and thus acts as a promising target in ischemia/reperfusion injury, cardioprotection, and neuroprotection [ 7 , 28 ]. The recycling of O -GlcNAc modification is highly dependent on the HBP pathway, which is a branch of nutrient metabolism, including glucose, glutamine, and glucosamine.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of O-GlcNAcylation on Mitochondrial Proteins with 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside, Contributes to the Mitochondrial Network, Cellular Bioenergetics and Stress Response in Neuronal Cells under Ischemic-like Conditions

Shen

et al. 2021

Molecules

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O-GlcNAcylation is a nutrient-driven post-translational modification known as a metabolic sensor that links metabolism to cellular function. Recent evidences indicate that the activation of O-GlcNAc pathway is a potential pro-survival pathway and that acute enhancement of this response is conducive to the survival of cells and tissues. 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside (SalA-4g), is a salidroside analogue synthesized in our laboratory by chemical structure-modification, with a phenyl ring containing a para-methoxy group and a sugar ring consisting of N-acetylglucosamine. We have previously shown that SalA-4g elevates levels of protein O-GlcNAc and improves neuronal tolerance to ischemia. However, the specific target of SalA-4g regulating O-GlcNAcylation remains unknown. To address these questions, in this study, we have focused on mitochondrial network homeostasis mediated by O-GlcNAcylation in SalA-4g’s neuroprotection in primary cortical neurons under ischemic-like conditions. O-GlcNAc-modified mitochondria induced by SalA-4g demonstrated stronger neuroprotection under oxygen glucose deprivation and reoxygenation stress, including the improvement of mitochondrial homeostasis and bioenergy, and inhibition of mitochondrial apoptosis pathway. Blocking mitochondrial protein O-GlcNAcylation with OSMI-1 disrupted mitochondrial network homeostasis and antagonized the protective effects of SalA-4g. Collectively, these data demonstrate that mitochondrial homeostasis mediated by mitochondrial protein O-GlcNAcylation is critically involved in SalA-4g neuroprotection.

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“…Later, in 1997, Järvinen et al ( Yki-Järvinen et al, 1997 ) reported a higher activity of OGT in the rat heart, compared to other tissues (liver, fat, striated muscle). Currently, a wide variety of studies show the participation of O -GlcNAc in the heart and vasculature ( Collins and Chatham, 2020 ). For example, O -GlcNAcylation shows dynamic and extensive cross-talk protein phosphorylation, including the mitogen-activated protein kinase (MAPK) pathway, and regulates various cellular signals and functions ( Zhang et al, 2015b ).…”

Section: O -Glycosylation: Type O -Glcnacylation On Heart and Vascular Wallmentioning

confidence: 99%

“…For example, O -GlcNAcylation shows dynamic and extensive cross-talk protein phosphorylation, including the mitogen-activated protein kinase (MAPK) pathway, and regulates various cellular signals and functions ( Zhang et al, 2015b ). Although some studies emphasized that O- GlcNAcylation provide significant cardio protection, higher O- GlcNAc levels increase vascular reactivity to constrictive stimulation, impair nitric oxide-dependent arteriolar dilations, reduce neointimal formation, prevent inflammation-induced vascular dysfunction, and modulate placental vasculogenesis ( Xing et al, 2008 ; Yang et al, 2015b ; Collins and Chatham, 2020 ). On the other hand, increased levels of O- GlcNAcylation may increase contractile responses in the rat basilar artery through activation of the MAPK pathway and, thus, may contribute to abnormal vascular reactivity; this was analyzed using Wistar rats, a group on a control diet (10% fat) and the other on a high-fat diet (45% fat) for 12 weeks ( Lima et al, 2016 ).…”

Section: O -Glycosylation: Type O -Glcnacylation On Heart and Vascular Wallmentioning

confidence: 99%

An Overview of Glycosylation and its Impact on Cardiovascular Health and Disease

Loaeza-Reyes

Zenteno

Moreno-Rodríguez

et al. 2021

Front. Mol. Biosci.

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The cardiovascular system is a complex and well-organized system in which glycosylation plays a vital role. The heart and vascular wall cells are constituted by an array of specific receptors; most of them are N- glycosylated and mucin-type O-glycosylated. There are also intracellular signaling pathways regulated by different post-translational modifications, including O-GlcNAcylation, which promote adequate responses to extracellular stimuli and signaling transduction. Herein, we provide an overview of N-glycosylation and O-glycosylation, including O-GlcNAcylation, and their role at different levels such as reception of signal, signal transduction, and exogenous molecules or agonists, which stimulate the heart and vascular wall cells with effects in different conditions, like the physiological status, ischemia/reperfusion, exercise, or during low-grade inflammation in diabetes and aging. Furthermore, mutations of glycosyltransferases and receptors are associated with development of cardiovascular diseases. The knowledge on glycosylation and its effects could be considered biochemical markers and might be useful as a therapeutic tool to control cardiovascular diseases.

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Regulation of cardiac O-GlcNAcylation: More than just nutrient availability

Cited by 22 publications

References 114 publications

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Enhancement of O-GlcNAcylation on Mitochondrial Proteins with 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside, Contributes to the Mitochondrial Network, Cellular Bioenergetics and Stress Response in Neuronal Cells under Ischemic-like Conditions

An Overview of Glycosylation and its Impact on Cardiovascular Health and Disease

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