Post-translational protein modification by O-linked N-acetyl-glucosamine: Its role in mediating the adverse effects of diabetes on the heart

McLarty, Jennifer L.; Marsh, Susan A.; Chatham, John C.

doi:10.1016/j.lfs.2012.08.006

Cited by 66 publications

(48 citation statements)

References 84 publications

(101 reference statements)

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“…Protein O-GlcNAcylation has been shown to be involved in numerous cellular processes including signal transduction, protein trafficking, protein-protein interactions, protein degradation, and regulation of gene expression and cell survival responses (12,72,145). Increased O-GlcNAc levels have also been implicated in contributing to the adverse effects of hyperglycemia in a wide range of tissues and cells, and sustained O-GlcNAcylation is now widely appreciated as a pathogenic mediator of diabetic complications (16,28,46,64).…”

Section: Potential Role For Stim1-mediated Soce In Ischemia/reperfusimentioning

confidence: 99%

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

Collins

Zhu-Mauldin

Marchase

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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108

102

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Collins HE, Zhu-Mauldin X, Marchase RB, Chatham JC. STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology. Am J Physiol Heart Circ Physiol 305: H446 -H458, 2013. First published June 21, 2013 doi:10.1152/ajpheart.00104.2013.-Store-operated Ca 2ϩ entry (SOCE) is critical for Ca 2ϩ signaling in nonexcitable cells; however, its role in the regulation of cardiomyocyte Ca 2ϩ homeostasis has only recently been investigated. The increased understanding of the role of stromal interaction molecule 1 (STIM1) in regulating SOCE combined with recent studies demonstrating the presence of STIM1 in cardiomyocytes provides support that this pathway co-exists in the heart with the more widely recognized Ca 2ϩ handling pathways associated with excitation-contraction coupling. There is now substantial evidence that STIM1-mediated SOCE plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo, and there is growing support for the contribution of SOCE to Ca 2ϩ overload associated with ischemia/reperfusion injury. Here, we provide an overview of our current understanding of the molecular regulation of SOCE and discuss the evidence supporting the role of STIM1/Orai1-mediated SOCE in regulating cardiomyocyte function.store-operated Ca 2ϩ entry; stromal interaction molecule 1; orai1; cardiomyocytes STORE-OPERATED CA 2ϩ ENTRY (SOCE), also known as capacitative calcium entry (CCE), is the major mechanism of Ca 2ϩ entry in nearly all nonexcitable cells (97, 99). In addition, it is increasingly recognized to co-exist with voltage-gated Ca 2ϩ channels in excitable cells, including neurons, skeletal muscle cells, and cardiomyocytes (1,38,45,83,121). In response to inositol 1,4,5-triphosphate (IP 3 )-(43) or ryanodine receptor (RyR)-mediated (3) Ca 2ϩ release from ER/SR stores, SOCE facilitates the influx of Ca 2ϩ from the extracellular space, resulting in a sustained increase in cytosolic Ca 2ϩ levels. Thus, although one of the roles of SOCE is to rapidly refill the depleted ER/SR stores, the subsequent sustained increase in cytosolic Ca 2ϩ also regulates numerous gene transcription pathways (33,50,151). Indeed, aberrant SOCE has been observed in a growing number of diseases including severe combined immunodeficiency, acute pancreatitis, and Alzheimer's disease (86).The integration of SOCE into well-established models of Ca 2ϩ homeostasis was hampered for many years by the lack of specific molecular mediators; even as recently as 2004 there was considerable controversy as to the specific mechanisms regulating SOCE (90, 113). However, in 2005, stromal interaction molecule 1 (STIM1) was found to localize to the ER/SR membrane and shown to function as a primary mediator of SOCE (54, 102). The putative physiological and pathophysiological roles of SOCE and STIM1 that have been identified to date are summarized in Table 1. A number of studies have recently reported the presence of STIM1 in adult cardiomyocytes (37,59,153), and consistent with earlier evidence supporting a rol...

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Section: Potential Role For Stim1-mediated Soce In Ischemia/reperfusimentioning

confidence: 99%

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

Collins

Zhu-Mauldin

Marchase

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

108

102

View full text Add to dashboard Cite

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“…Since then, much work has been published elucidating the role of O-GlcNAc modification in many biological processes, including nuclear transport, transcription and translation, cytoskeletal organization, signal transduction, proteasomal function and cell survival, and most recently cardiac dysfunction [58][59][60][61][62]. However, the exact role of O-GlcNAc in mediating DHD, and specifically O-GlcNAc modification of CaMKIId, is not fully understood [63].…”

Section: O-glcnac Modification and Camkiid Activitymentioning

confidence: 99%

“…Therefore, the elevated plasma glucose levels in diabetes potentially suggest a possible mechanistic link between protein O-GlcNAcylation and DHD [63]. Medford et al [65] reported that a 'western diet' high in saturated fat and sugar, which has long been associated with type II diabetes, results in increased OGlcNAcylation of cardiac proteins.…”

Section: O-glcnac Modification and Camkiid Activitymentioning

confidence: 99%

The role of CaMKII in diabetic heart dysfunction

et al. 2015

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Diabetes mellitus (DM) is an increasing epidemic that places a significant burden on health services worldwide. The incidence of heart failure (HF) is significantly higher in diabetic patients compared to non-diabetic patients. One underlying mechanism proposed for the link between DM and HF is activation of calmodulin-dependent protein kinase (CaMKIIδ). CaMKIIδ mediates ion channel function and Ca(2+) handling during excitation-contraction and excitation-transcription coupling in the myocardium. CaMKIIδ activity is up-regulated in the myocardium of diabetic patients and mouse models of diabetes, where it promotes pathological signaling that includes hypertrophy, fibrosis and apoptosis. Pharmacological inhibition and knockout models of CaMKIIδ have shown some promise of a potential therapeutic benefit of CaMKIIδ inhibition, with protection against cardiac hypertrophy and apoptosis reported. This review will highlight the pathological role of CaMKIIδ in diabetes and discuss CaMKIIδ as a therapeutic target in DM, and also the effects of exercise on CaMKIIδ.

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“…Thus, hyperglycaemia, a hallmark of diabetes, may increase flux through the HBP and consequently promote protein O-GlcNAcylation [22–25]. Indeed, several studies suggest that protein O-GlcNAcylation contributes to various aspects of cellular dysfunction during diabetes [10–14,16– 18,25–31]. In contrast, acute protein O-GlcNAcylation confers protection in the context of cell stress [20,32–43].…”

Section: Introductionmentioning

confidence: 99%

High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation

Dassanayaka

Readnower

Salabei

et al. 2015

Biochemical Journal

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Diabetes is characterized by hyperglycaemia and perturbations in intermediary metabolism. In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. Diabetes also promotes mitochondrial dysfunction. Nevertheless, the relationships among diabetes, hyperglycaemia, mitochondrial dysfunction and O-GlcNAc modifications remain unclear. In the present study, we tested whether high-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P < 0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. Furthermore, an osmotic control recapitulated high-glucose-induced changes to mitochondrial metabolism (P < 0.05) without increasing O-GlcNAcylation. Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes.

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Post-translational protein modification by O-linked N-acetyl-glucosamine: Its role in mediating the adverse effects of diabetes on the heart

Cited by 66 publications

References 84 publications

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

The role of CaMKII in diabetic heart dysfunction

High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation

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