Serum Glutathione S-Transferase P1 1 in Prediction of Cardiac Function

Andrukhova, Olena; Salama, Mohamed; Rosenhek, Raphaël; Gmeiner, Matthias; Perkmann, Thomas; Steindl, Johannes; Aharinejad, Seyedhossein

doi:10.1016/j.cardfail.2011.11.003

Cited by 16 publications

(9 citation statements)

References 23 publications

(26 reference statements)

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“…Thus, our studies showing that GSTP is a cardioprotective gene could form the basis of future studies to investigate the role of human GSTP1 polymorphisms in clinical outcomes of acute myocardial infarction and heart failure. 59 …”

Section: Discussionmentioning

confidence: 99%

Genetic Deficiency of Glutathione S -Transferase P Increases Myocardial Sensitivity to Ischemia–Reperfusion Injury

Conklin¹,

Guo²,

Jagatheesan³

et al. 2015

Circulation Research

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Rationale Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. Objective We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury. Methods and Results In adult male C57BL/6 mouse hearts, Gstp1/2 was the most abundant GST transcript followed by Gsta4 and Gstm4.1, and GSTP activity was a significant fraction of the total GST activity. mGstp1/2 deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type (WT) mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism 4-hydroxy-trans-2-nonenal (HNE) or trans-2-hexanal; and, upon ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than WT hearts. GSTP-deficiency did not affect I/R-induced free radical generation, JNK activation or depletion of reduced glutathione. Acrolein-exposure induced a hyperpolarizing shift in INa, and acrolein-induced cell death was delayed by SN-6, a Na+/Ca++ exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than WT myocytes to acrolein-induced protein crosslinking and cell death. Conclusions GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes such as acrolein.

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Section: Discussionmentioning

confidence: 99%

Genetic Deficiency of Glutathione S -Transferase P Increases Myocardial Sensitivity to Ischemia–Reperfusion Injury

Conklin¹,

Guo²,

Jagatheesan³

et al. 2015

Circulation Research

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“…A major regulator of the AREs is the highly conserved transcription factor, nuclear factor-erythroid-2- (NF-E2-) related factor 2 (Nrf2). Many of the Nrf2-regulated enzymes are essential in the pathogenesis of cardiovascular diseases [ 17 ] and are strongly associated with HF; in addition, they serve as sensitive and specific markers to reflect the ventricular function in HF patients [ 18 ]. Nrf2 also can prolong graft survival and modulate innate and adaptive immune responses after heart transplantation [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

Zhou

Sun

Zhang

et al. 2014

Oxidative Medicine and Cellular Longevity

149

135

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Heart failure (HF) is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS) in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2-) related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF.

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“…rs1332018 (C/A), rs1799735 (del/AGG) of GSTM3 [21]; GSTP1 Ala114Val (GSTP1*A/*B/*C/*D) [15,24,30]; GSTP1 C341T [24] and GSTO1 rs1804834 [27,31] were also reported in AD. We did not perform any pooled analysis on these SNPs in AD because the relevant studies were limited.…”

Section: Discussionmentioning

confidence: 93%

Glutathione S-transferases variants as risk factors in Alzheimer’s disease

Wang

2015

Neurol Sci

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Glutathione S-transferase (GST) was suggested as an important contributor to Alzheimer's disease (AD). The GSTs polymorphisms have been investigated as candidate genetic risk factors for AD, yet results remained uncertain. Therefore, we performed a meta-analysis to clarify the relationship of GSTs polymorphisms with the occurrence of AD. PubMed, Embase, Cochrane library and Alzgene databases were searched and potential literatures were selected. Pooled analyses and subgroup analyses were conducted, and also publication bias tests and cumulative meta-analysis. This meta-analysis suggested null associations between polymorphisms of GSTM1, GSTT1, GSTM3, GSTP1, GSTO1 and AD risk. GSTs variants may not have an impact on the morbidity of Alzheimer's disease. Further well designed researches are required to confirm these findings of the current study.

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Serum Glutathione S-Transferase P1 1 in Prediction of Cardiac Function

Cited by 16 publications

References 23 publications

Genetic Deficiency of Glutathione S -Transferase P Increases Myocardial Sensitivity to Ischemia–Reperfusion Injury

Genetic Deficiency of Glutathione S -Transferase P Increases Myocardial Sensitivity to Ischemia–Reperfusion Injury

The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

Glutathione S-transferases variants as risk factors in Alzheimer’s disease

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