Ischemic preconditioning increases myocardial O-GlcNAc glycosylation

Jensen, Rebekka Vibjerg; Johnsen, Jacob; Kristiansen, Steen Buus; Zachara, Natasha E.; Bøtker, Hans Erik

doi:10.3109/14017431.2012.756984

Cited by 32 publications

(25 citation statements)

References 18 publications

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“…It is possible, therefore, that these approaches may be more effective than those focused on glucose and insulin. In this context it is somewhat surprising that given the early success of increasing O-GlcNAc levels in vitro and in vivo murine model systems of I/R [21–23], that this has not been translated into studies in larger animal models. One hurdle for continued studies has been defining the specific pathways contributing to the changes.…”

Section: Ischemia/reperfusion Injurymentioning

confidence: 99%

O-GlcNAcylation and cardiovascular disease

Wright

Collins

Wende

et al. 2017

Biochemical Society Transactions

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The post-translational modification of serine and threonine residues of proteins found in the numerous sub-cellular locations by O-linked N-acetylglucosamine (O-GlcNAc) is emerging as a key mediator of a number of cardiovascular pathophysiological processes. Early studies implicated increased protein O-GlcNAcylation as contributing to the cardiovascular complications associated with diabetes; whereas, subsequent studies demonstrated that acute increases in O-GlcNAc levels were protective against ischemia/reperfusion injury. There is now growing understanding that O-GlcNAc modification of proteins influences numerous cellular functions, including transcription, protein turnover, calcium handling, and bioenergetics. As a result, a more nuanced view of the role of protein O-GlcNAcylation in the cardiovascular system is emerging along with the recognition that it is required for normal cellular function and homeostasis. Consequently, the impact of changes in O-GlcNAc cycling due to stress or disease on the heart is complex and highly dependent on the specific context of these events. The goal of this review is to provide an overview of some of the more recent advances in our understanding of the role O-GlcNAcylation plays in mediating cardiovascular function and disease.

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Section: Ischemia/reperfusion Injurymentioning

confidence: 99%

O-GlcNAcylation and cardiovascular disease

Wright

Collins

Wende

et al. 2017

Biochemical Society Transactions

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“…It was shown that acute induction of the hexosamine pathway through the spliced transcription factor Xbp1s, which acts upstream of the HP, leads to organ protection in a mouse model of cardiac ischemia-reperfusion injury (IR) [9]. Moreover, Jensen et al suggested that the protective effects of remote ischemic (RIPC) and ischemic preconditioning (IPC) are due to increased circulating GlcNAc levels and O-GlcNAcylation, as well [10]. The positive effects of the HP do not appear to be limited to the heart since GlcNAc administration before and especially after ischemia of the eye has been shown to mediate retinal cell survival [11].…”

Section: Introductionmentioning

confidence: 99%

Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

et al. 2016

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Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney.

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“…At the end of reperfusion hearts were frozen at − 80 °C for 15 min, sliced (≈ 1.5 mm), and stained with 1% 2.3.5-triphenyltetrazolium chloride, for 3 min at 37 °C and pH 7.4 as previously described [ 23 ]. After each slice was weighed and scanned (Epson Perfection V600, Epson, Nagano, Japan) the area of whole slice minus cavities, area at risk (AAR) and area of infarction (IS) were assessed by computer planimetry (UTHSCA ImageTool, San Antonio, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

Effects of hypoglycemia on myocardial susceptibility to ischemia–reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes

Pælestik

Jespersen

Jensen

et al. 2017

Cardiovasc Diabetol

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BackgroundHypoglycemia is associated with increased mortality rate in patients with diabetes. The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC). As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc). We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.MethodsIn a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6–7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l]. Myocardial glucose uptake and O-GlcNAc levels were evaluated during reperfusion. IPC was induced by 2 × 5 min of global ischemia prior to index ischemia.ResultsIS increased in hearts from animals with (p < 0.01) and without (p < 0.01) diabetes during hypoglycemia compared to normoglycemia. IPC reduced IS during normoglycemia in both animals with (p < 0.01) and without (p < 0.01) diabetes. During hypoglycemia, however, IPC only reduced IS in hearts from animals with diabetes (p < 0.05). IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).ConclusionsHypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes. In contrast to hearts from animals without diabetes, the hearts from animals with diabetes are amenable to cardioprotection during hypoglycemia. In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.

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Ischemic preconditioning increases myocardial O-GlcNAc glycosylation

Cited by 32 publications

References 18 publications

O-GlcNAcylation and cardiovascular disease

O-GlcNAcylation and cardiovascular disease

Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

Effects of hypoglycemia on myocardial susceptibility to ischemia–reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes

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