High glucose sensitizes adult cardiomyocytes to ischaemia/reperfusion injury through nitrative thioredoxin inactivation

Luan, Rongsheng; Liu, Shaowei; Yin, Tao; Lau, Wayne Bond; Wang, Qiong; W, Guo; Wang, Haichang; Tao, Ling

doi:10.1093/cvr/cvp085

Cited by 51 publications

(23 citation statements)

References 29 publications

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“…This suggests that hyperglycemia sensitizes cardiomyocytes to a hypertrophic response, and that addition of a further strain such as osmotic pressure or oxidative stress is needed to activate the hypertrophic response. Consistent with this, cardiomyocytes cultured in high glucose are more sensitive to acute stress such as I/R injury (99). This is likely due to a combination of factors, including mitochondrial sensitization, osmotic stress, oxidation of cellular components by ROS, and decreased autophagy.…”

Section: Etiology and Pathogenesis Of Diabetic Cardiomyopathysupporting

confidence: 67%

Unbreak My Heart: Targeting Mitochondrial Autophagy in Diabetic Cardiomyopathy

Kubli

Gustafsson

2015

Antioxidants & Redox Signaling

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Significance: Diabetes is strongly associated with increased incidence of heart disease and mortality due to development of diabetic cardiomyopathy. Even in the absence of cardiovascular disease, cardiomyopathy frequently arises in diabetic patients. Current treatment options for cardiomyopathy in diabetic patients are the same as for nondiabetic patients and do not address the causes underlying the loss of contractility. Recent Advances: Although there are numerous distinctions between Type 1 and Type 2 diabetes, recent evidence suggests that the two disease states converge on mitochondria as an epicenter for cardiomyocyte damage. Critical Issues: Accumulation of dysfunctional mitochondria contributes to cardiac tissue injury in both acute and chronic conditions. Removal of damaged mitochondria by macroautophagy, termed ''mitophagy,'' is critical for maintaining cardiomyocyte health and contractility both under normal conditions and during stress. However, very little is known about the involvement of mitophagy in the pathogenesis of diabetic cardiomyopathy. A growing interest in this topic has given rise to a wave of publications that aim at deciphering the status of autophagy and mitophagy in Type 1 and Type 2 diabetes. Future Directions: This review summarizes these recent studies with the goal of drawing conclusions about the activation or suppression of autophagy and mitophagy in the diabetic heart. A better understanding of how autophagy and mitophagy are affected in the diabetic myocardium is still needed, as well as whether they can be targeted therapeutically. Antioxid. Redox Signal. 22, 1527Signal. 22, -1544

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Section: Etiology and Pathogenesis Of Diabetic Cardiomyopathysupporting

confidence: 67%

Unbreak My Heart: Targeting Mitochondrial Autophagy in Diabetic Cardiomyopathy

Kubli

Gustafsson

2015

Antioxidants & Redox Signaling

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“…The relationship between diabetic complications and oxidative and/or nitrosative stress is believed to be related to increased superoxide generation and 3-NT accumulation (2,16). In this study, we confirmed that high levels of superoxide and 3-NT accompany development of cardiac remodeling in the late stage of diabetes.…”

Section: Discussionsupporting

confidence: 81%

Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp³⁷⁴

Cong

Zhao

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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L. Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp 374 . Am J Physiol Endocrinol Metab 304: E826 -E835, 2013. First published February 26, 2013 doi:10.1152/ajpendo.00570.2012.-We previously demonstrated that metallothionein (MT)-mediated protection from diabetesinduced pathological changes in cardiac tissues is related to suppression of superoxide generation and protein nitration. The present study investigated which diabetes-nitrated protein(s) mediate the development of these pathological changes by identifying the panel of nitrated proteins present in diabetic hearts of wild-type (WT) mice and not in those of cardiac-specific MT-overexpressing transgenic (MT-TG) mice. At 2, 4, 8, and 16 wk after streptozotocin induction of diabetes, histopathological examination of the WT and MT-TG diabetic hearts revealed cardiac structure derangement and remodeling, significantly increased superoxide generation, and 3-nitrotyrosine accumulation. A nitrated protein of 58 kDa, succinyl-CoA:3-ketoacid CoA transferase-1 (SCOT), was identified by mass spectrometry. Although total SCOT expression was not significantly different between the two types of mice, the diabetic WT hearts showed significantly increased nitration content and dramatically decreased catalyzing activity of SCOT. Although SCOT nitration sites were identified at diabetes; cardiac pathological changes; metallothionein; SCOT; 3-nitrotyrosine DIABETES HAS BECOME one of the most prolific public health issues worldwide (25). Mechanistic studies have revealed that oxidative and nitrosative stress are major causes of diabetes and its complications (4, 13). Overproduced superoxide has been shown in diabetic individuals to interact with nitric oxide, forming the peroxynitrite (ONOO Ϫ ) free radical that mediates biomacromolecule nitration and can ultimately lead to organ dysfunction. The covalent product of tyrosine nitration, 3-nitrotyrosine (3-NT), serves as an index of peroxynitrite-induced protein damage and is used in clinic as a convenient quantitative biomarker of cardiovascular risk (measured in free and protein-bound forms in human plasma) (23). Moreover, overproduction of superoxide and associated peroxynitrite has been implicated in the development of diabetic cardiomyopathy (4, 20, 28). Therefore, a promising approach to prevent the development of diabetic complications will include the prevention of oxidative and nitrosative stress (2).The well-established and widely used animal model of type 1 diabetes induced by streptozotocin (STZ) has several nitrated molecules in the cardiac tissue. The majority of these nitrated molecules are mitochondrial proteins with known functions in cellular energy metabolism and oxygen oxidation (26,27,29). However, whether the nitration of these mitochondrial proteins contributes to the development of diabetic cardiomyopathy remains largely unknown.The cysteine-rich protein metallothionein (MT) is a ubiquito...

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“…In this study, Trx-1 also reduced peroxynitrite donor SIN-1 (3-morpholinosydnonimine)-induced cardiomyocyte apoptosis. In another study, high glucose was found to sensitize cardiomyocytes to ischemia=reperfusion injury due to nitrative inactivation of Trx-1 (108). The treatment of cardiomyocytes with rhTrx-1 exerts its cardioprotective effect by suppressing the ischemia=reperfusion-induced nitrative stress (176).…”

Section: Thioredoxin and Related Molecules As Biomarkers Of Cardiovasmentioning

confidence: 96%

Redox Regulation of Cell Survival by the Thioredoxin Superfamily: An Implication of Redox Gene Therapy in the Heart

Ahsan

Lekli

Ray

et al. 2009

Antioxidants & Redox Signaling

111

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Reactive oxygen species (ROS) are the key mediators of pathogenesis in cardiovascular diseases. Members of the thioredoxin superfamily take an active part in scavenging reactive oxygen species, thus playing an essential role in maintaining the intracellular redox status. The alteration in the expression levels of thioredoxin family members and related molecules constitute effective biomarkers in various diseases, including cardiovascular complications that involve oxidative stress. Thioredoxin, glutaredoxin, peroxiredoxin, and glutathione peroxidase, along with their isoforms, are involved in interaction with the members of metabolic and signaling pathways, thus making them attractive targets for clinical intervention. Studies with cells and transgenic animals have supported this notion and raised the hope for possible gene therapy as modern genetic medicine. Of all the molecules, thioredoxins, glutaredoxins, and peroxiredoxins are emphasized, because a growing body of evidence reveals their essential and regulatory role in several steps of redox regulation. In this review, we discuss some pertinent observations regarding their distribution, structure, functions, and interactions with the several survival-and death-signaling pathways, especially in the myocardium. Antioxid. Redox Signal. 11, 2741-2758.

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High glucose sensitizes adult cardiomyocytes to ischaemia/reperfusion injury through nitrative thioredoxin inactivation

Abstract: High glucose sensitized cardiomyocytes to ischaemia/reperfusion injury through nitrative Trx-1 inactivation. Interventions restoring Trx-1 activity in the diabetic heart may represent novel therapies attenuating cardiac injury in diabetic patients.

Cited by 51 publications

References 29 publications

Unbreak My Heart: Targeting Mitochondrial Autophagy in Diabetic Cardiomyopathy

Unbreak My Heart: Targeting Mitochondrial Autophagy in Diabetic Cardiomyopathy

Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp³⁷⁴

Redox Regulation of Cell Survival by the Thioredoxin Superfamily: An Implication of Redox Gene Therapy in the Heart

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High glucose sensitizes adult cardiomyocytes to ischaemia/reperfusion injury through nitrative thioredoxin inactivation

Abstract: High glucose sensitized cardiomyocytes to ischaemia/reperfusion injury through nitrative Trx-1 inactivation. Interventions restoring Trx-1 activity in the diabetic heart may represent novel therapies attenuating cardiac injury in diabetic patients.

Cited by 51 publications

References 29 publications

Unbreak My Heart: Targeting Mitochondrial Autophagy in Diabetic Cardiomyopathy

Unbreak My Heart: Targeting Mitochondrial Autophagy in Diabetic Cardiomyopathy

Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp374

Redox Regulation of Cell Survival by the Thioredoxin Superfamily: An Implication of Redox Gene Therapy in the Heart

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Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp³⁷⁴