Increased hexosamine biosynthesis and protein O-GlcNAc levels associated with myocardial protection against calcium paradox and ischemia

Liu, Jia; Pang, Yi; Chang, Theresa L.; Bounelis, Pam; Chatham, John C.; Marchase, Richard B.

doi:10.1016/j.yjmcc.2005.11.003

Cited by 160 publications

(184 citation statements)

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“…Therefore, in light of the growing evidence linking TRPC proteins to CCE in cardiomyocytes, combined with our finding that CCE inhibition attenuated cardiac injury in response to calcium overload (20), we tested the hypothesis that increased expression of TRPC3 in cardiomyocytes would result in increased injury due to I/R. We found that TRPC3 overexpression increased apoptosis and calpain-mediated proteolysis resulting from I/R injury and also increased sensitivity to Ca 2ϩ overload; however, TRPC3 had no effect on the response to TNF-␣-induced apoptosis.…”

mentioning

confidence: 60%

“…Although a number of Ca 2ϩ entry pathways, including the Na ϩ /Ca 2ϩ exchanger and the L-type Ca 2ϩ channel, have been implicated in mediating cardiomyocyte Ca 2ϩ overload (4,6,32), there is little consensus as to which pathways are critical in mediating this process. We have identified a capacitative calcium entry (CCE) or store-operated calcium entry pathway in neonatal and adult rat cardiomyocytes (12,13) that not only influences the response to hypertrophic stimuli but may also play a role in mediating Ca 2ϩ overload in the heart (20). CCE or store-operated calcium, which was first described in nonexcitable cells (34), refers to the influx of Ca 2ϩ through plasma membrane calcium channels, activated in response to depletion of calcium in the endo/sarcoplasmic reticulum.…”

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confidence: 99%

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Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Shan

Marchase²,

Chatham

2008

American Journal of Physiology-Cell Physiology

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Shan D, Marchase RB, Chatham JC. Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes. Am J Physiol Cell Physiol 294: C833-C841, 2008. First published January 9, 2008 doi:10.1152/ajpcell.00313.2007.-An increase in cytosolic Ca 2ϩ via a capacitative calcium entry (CCE)-mediated pathway, attributed to members of the transient receptor potential (TRP) superfamily, TRPC1 and TRPC3, has been reported to play an important role in regulating cardiomyocyte hypertrophy. Increased cytosolic Ca 2ϩ also plays a critical role in mediating cell death in response to ischemiareperfusion (I/R). Therefore, we tested the hypothesis that overexpression of TRPC3 in cardiomyocytes will increase sensitivity to I/R injury. Adult cardiomyocytes isolated from wild-type (WT) mice and from mice overexpressing TRPC3 in the heart were subjected to 90 min of ischemia and 3 h of reperfusion. After I/R, viability was 51 Ϯ 1% in WT mice and 42 Ϯ 5% in transgenic mice (P Ͻ 0.05). Apoptosis assessed by annexin V was significantly increased in the TRPC3 group compared with WT (32 Ϯ 1% vs. 21 Ϯ 3%; P Ͻ 0.05); however, there was no significant difference in necrosis between groups. Treatment of TRPC3 cells with the CCE inhibitor SKF-96365 (0.5 M) significantly improved cellular viability (54 Ϯ 4%) and decreased apoptosis (15 Ϯ 4%); in contrast, the L-type Ca 2ϩ channel inhibitor verapamil (10 M) had no effect. Calpain-mediated cleavage of ␣-fodrin was increased approximately threefold in the transgenic group following I/R compared with WT (P Ͻ 0.05); this was significantly attenuated by SKF-96365. The calpain inhibitor PD-150606 (25 M) attenuated the increase in both ␣-fodrin cleavage and apoptosis in the TPRC3 group. Increased TRPC3 expression also increased sensitivity to Ca 2ϩ overload stress, but it did not affect the response to TNF-␣-induced apoptosis. These results suggest that CCE mediated via TRPC may play a role in cardiomyocyte apoptosis following I/R due, at least in part, to increased calpain activation.

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confidence: 60%

mentioning

confidence: 99%

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Shan

Marchase²,

Chatham

2008

American Journal of Physiology-Cell Physiology

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“…Recent data suggests that O-GlcNAc is one component of the cellular stress response that is relevant to a variety of models of injury in several cell and tissue types. OGlcNAc levels become elevated in response to numerous forms of cell stress and tissue injury including: heat stress (Sohn et al 2004;Zachara et al 2004b), oxidative stress Zachara et al 2004b), ethanolic stress (Zachara et al 2004b;Ngoh et al 2009b), genotoxic stress (doxorubicin, belocin, and UVB irradiation; Zachara et al 2004bZachara et al , 2011aLove et al 2010), reductive stress (iodoacetamide; Zachara et al 2004b), ER stress (dithiothreitol and tunicamycin; Zachara et al 2004b;Ngoh et al 2009b), hypoxia reoxygenation (Ngoh et al 2009a;Ngoh et al 2008;Ngoh et al 2011), osmotic stress (NaCl, sorbitol, and sucrose; Zachara et al 2004b;Zou et al 2007), ATP depletion (sodium arsenite; Zachara et al 2004b), ischemia reperfusion injury (Champattanachai et al 2007(Champattanachai et al , 2008Fulop et al 2007a, b;Hwang et al 2010;Jones et al 2008;Laczy et al 2010;Liu et al 2006Liu et al , 2007Nagy et al 2006;Ngoh et al 2008Ngoh et al , 2009aNgoh et al , b, 2011Pang et al 2002;Zou et al 2009), and trauma hemorrhage Yang et al 2006a;Zou et al 2007Zou et al , 2009). This response occurs in primary and transformed cells, as well as in tissues in vivo and ex vivo.…”

Section: O-glcnac and The Cellular Stress Responsementioning

confidence: 99%

“…Some examples include: (1) increased protein solubility during heat stress Lim and Chang 2006) or Alzheimer's disease (Yuzwa et al 2012); (2) reduced calcium overload (Liu et al 2006(Liu et al , 2007; (3) decreased calpain activation (Liu et al 2007); (4) altered p38 MAPK activation in response to ischemia reperfusion injury (Fulop et al 2007b;; (5) modulation of proinflammatory cytokines (Huang et al 2007;Zou et al 2009); (6) reduced mitochondrial permeability transition pore (mPTP) formation ); (7) increased B-cell lymphoma 2 (Bcl-2) expression and translocation (Champattanachai et al 2008); and (8) regulation of the expression of a subset of molecular chaperones (Zachara et al 2004b;Kazemi et al 2010;Sohn et al 2004).…”

Section: O-glcnac and The Cellular Stress Responsementioning

confidence: 99%

“…For example, O-GlcNAc appears to regulate many of the hallmarks of I/R injury such as calcium overload, oxidative damage, ER stress, and mitochondrial aberrations . Elevating OGlcNAc levels with glucosamine, PUGNAc (O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate), or thiamet G (TMG, 2-ethylamino-3aR, 6S, 7R, 7aR-tetrahydro-5R-hydroxymethyl-5H-pyrano[3, 2-d]thiazole-6, 7-diol) leads to improved function and reduced tissue death in both ex vivo and in vivo models of I/R injury in the heart (Liu et al 2007;Liu et al 2006;Fulop et al 2007b;Jones et al 2008). Collectively, these data suggest that the stress-induced elevation of the O-GlcNAc modification is a pro-survival response of cells and tissues (Champattanachai et al 2007(Champattanachai et al , 2008Hwang et al 2010).…”

Section: O-glcnac and The Cellular Stress Responsementioning

confidence: 99%

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Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Groves

Lee

Yildirir

et al. 2013

Cell Stress and Chaperones

120

112

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O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) is a ubiquitous and dynamic post-translational modification known to modify over 3,000 nuclear, cytoplasmic, and mitochondrial eukaryotic proteins. Addition of O-GlcNAc to proteins is catalyzed by the O-GlcNAc transferase and is removed by a neutral-N-acetyl-β-glucosaminidase (OGlcNAcase). O-GlcNAc is thought to regulate proteins in a manner analogous to protein phosphorylation, and the cycling of this carbohydrate modification regulates many cellular functions such as the cellular stress response. Diverse forms of cellular stress and tissue injury result in enhanced O-GlcNAc modification, or O-GlcNAcylation, of numerous intracellular proteins. Stress-induced OGlcNAcylation appears to promote cell/tissue survival by regulating a multitude of biological processes including: the phosphoinositide 3-kinase/Akt pathway, heat shock protein expression, calcium homeostasis, levels of reactive oxygen species, ER stress, protein stability, mitochondrial dynamics, and inflammation. Here, we will discuss the regulation of these processes by O-GlcNAc and the impact of such regulation on survival in models of ischemia reperfusion injury and trauma hemorrhage. We will also discuss the misregulation of O-GlcNAc in diseases commonly associated with the stress response, namely Alzheimer's and Parkinson's diseases. Finally, we will highlight recent advancements in the tools and technologies used to study the O-GlcNAc modification.

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Critical observations that shaped our understanding of the function(s) of intracellular glycosylation (O‐GlcNAc)

Zachara

2018

FEBS Letters

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Almost 100 years after the first descriptions of proteins conjugated to carbohydrates (mucins), several studies suggested that glycoproteins were not restricted to the serum, extracellular matrix, cell surface, or endomembrane system. In the 1980’s, key data emerged demonstrating that intracellular proteins were modified by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc). Subsequently, this modification was identified on thousands of proteins that regulate cellular processes as diverse as protein aggregation, localization, post-translational modifications, activity, and interactions. In this Review, we will highlight critical discoveries that shaped our understanding of the molecular events underpinning the impact of O-GlcNAc on protein function, the role that O-GlcNAc plays in maintaining cellular homeostasis, and our understanding of the mechanisms that regulate O-GlcNAc-cycling.

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Increased hexosamine biosynthesis and protein O-GlcNAc levels associated with myocardial protection against calcium paradox and ischemia

Cited by 160 publications

References 47 publications

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Critical observations that shaped our understanding of the function(s) of intracellular glycosylation (O‐GlcNAc)

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