Tissue transglutaminase (TG2) protects cardiomyocytes against ischemia/reperfusion injury by regulating ATP synthesis

Szondy, Zsuzsa; Mastroberardino, Pier G.; Váradi, Judit; Farrace, Maria Grazia; Nagy, Norbert; Bak, István; Viti, I; Wieckowski, Mariusz R.; Melino, Gerry; Rizzuto, Rosario; Tósaki, Árpád; Fésüs, L.; Piacentini, Mauro

doi:10.1038/sj.cdd.4401889

Cited by 59 publications

(63 citation statements)

References 7 publications

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“…Instead, the increased susceptibility to injury appeared to be due to lower baseline stores of high energy phosphates in the TG2 null mice. TG2−/− mice have a mitochondrial functional defect with impaired ATPase function (178). These studies provide evidence for a novel role of TG2 in maintenance of mitochondrial respiratory function.…”

Section: Effect Of Tg2 On Cardiac Ischemia/reperfusion Injurymentioning

confidence: 66%

“…The cross-linking of TnT by TG2 occurs with apoptosis (177). Infarct size and the occurrence of ventricular fibrillation is significantly increased in TG2−/− ischemia/reperfused isolated hearts as compared to ischemia/reperfused wild-type hearts (178). The increased sensitivity of TG2 null mice to I/R injury is not due to impaired adrenergic receptor signaling.…”

Section: Effect Of Tg2 On Cardiac Ischemia/reperfusion Injurymentioning

confidence: 73%

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Roles of transglutaminases in cardiac and vascular diseases

Sane

Kontos²,

Greenberg³

2007

Front Biosci

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All transglutaminases share the common enzymatic activity of transamidation, or the cross-linking of glutamine and lysine residues to form N epsilon (gamma-glutamyl) lysyl isopeptide bonds. The plasma proenzyme factor XIII is responsible for stabilizing the fibrin clot against physical and fibrinolytic disruption. Another member of the transglutaminase family, tissue transglutaminase or TG2 is abundantly expressed in cardiomyocytes, vascular cells and macrophages. The transglutaminases have a variety of functions independent of their transamidating activity. For example, TG2 binds and hydrolyzes GTP, thereby fostering signal transduction by several G protein coupled receptors. Accumulating evidence points to novel roles for factor XIII and TG2 in cardiovascular biology including: (a) modulating platelet activity, (b) regulating glucose control, (c) contributing to the development of hypertension, (d) influencing the progression of atherosclerosis, (e) regulating vascular permeability and angiogenesis (f) and contributing to myocardial signaling, contractile activity and ischemia/reperfusion injury. In this review, we summarize the cardiovascular biology of two members of the family of transglutaminases, Factor XIII and TG2.

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Section: Effect Of Tg2 On Cardiac Ischemia/reperfusion Injurymentioning

confidence: 66%

Section: Effect Of Tg2 On Cardiac Ischemia/reperfusion Injurymentioning

confidence: 73%

Roles of transglutaminases in cardiac and vascular diseases

Sane

Kontos²,

Greenberg³

2007

Front Biosci

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“…14 Recently, we showed that TG2 À/À cardiomyocytes result more sensitive to ischemia/reperfusion injury than their wild-type counterparts. 15 In addition, we observed a significant decrease in the levels of adenine nucleotide in the hearts of TG2 À/À mice, as the result of an impaired mitochondrial function. 16 These results highlighted an unexpected role for TG2 in the modulation of mitochondrial physiology.…”

mentioning

confidence: 76%

“…18 It is interesting to note that TG2 À/À mice are particularly sensitive to ischemia/reperfusion, as a consequence of their impairment of ATP homoeostasis. 15 Furthermore, recent findings support an important role for ANT1 defects in the development of Type II diabetes, which has been associated with an increased ROS production. 13 We show here that TG2's protein PDI activity is physiologically involved in the maintenance of the mitochondrial physiology, by modulating the level of ANT1 polymers in the heart.…”

Section: Discussionmentioning

confidence: 99%

The adenine nucleotide translocator 1 acts as a type 2 transglutaminase substrate: implications for mitochondrial-dependent apoptosis

Malorni¹,

Farrace

Matarrese³

et al. 2009

Cell Death Differ

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In this study we provide in vitro and in vivo evidence showing that the protein disulphide isomerase (PDI) activity of type 2 transglutaminase (TG2) regulates the correct assembly and function of the mitochondrial ADP/ATP transporter adenine nucleotide translocator 1 (ANT1). We demonstrate, by means of biochemical and morphological analyses, that ANT1 and TG2 physically interact in the mitochondria. Under physiological conditions, TG2's PDI activity regulates the ADP/ATP transporter function by controlling the oligomerization of ANT1. In fact, mitochondria isolated from hearts of TG2 À/À mice exhibit increased polymerization of ANT1, paralleled by an enhanced ADP/ATP carrier activity, as compared to mitochondria belonging to TG2 þ / þ mice. Interestingly, upon cell-death induction, ANT1 becomes a substrate for TG2's cross-linking activity and the lack of TG2 results in a reduction of apoptosis as well as in a marked sensitivity to the ADP/ATP exchange inhibition by atractyloside. These findings suggest a complex TG2-dependent regulation of the ADP/ATP transporter and reveal new important avenues for its potential applications in the treatment of some mitochondrial-dependent diseases, including cardiovascular and neurodegenerative diseases.

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“…Tissue transglutaminase 2 protects cardiomyocytes against ischaemia-reperfusion injury by regulating ATP synthesis [588]. There is up-regulation of P2X7R in rat superior cervical ganglia (SCG) after myocardial ischaemic injury [589].…”

Section: Ischaemiamentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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Tissue transglutaminase (TG2) protects cardiomyocytes against ischemia/reperfusion injury by regulating ATP synthesis

Cited by 59 publications

References 7 publications

Roles of transglutaminases in cardiac and vascular diseases

Roles of transglutaminases in cardiac and vascular diseases

The adenine nucleotide translocator 1 acts as a type 2 transglutaminase substrate: implications for mitochondrial-dependent apoptosis

Cardiac purinergic signalling in health and disease

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