Rac1 Is Required for Cardiomyocyte Apoptosis During Hyperglycemia

Shen, Enhui; Li, Yanwen; Liu, Ying; Shan, Limei; Zhu, Huaqing; Feng, Qingping; Arnold, J. Malcolm O.; Peng, Tianqing

doi:10.2337/db08-0617

Cited by 172 publications

(175 citation statements)

References 51 publications

(81 reference statements)

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“…Apoptosis-Apoptosis was determined by assessing caspase-3 activity and TUNEL staining positive cells as described previously (35).…”

Section: Real-time Reverse Transcription-polymerase Chain Reaction (Rmentioning

confidence: 99%

Deficiency of Capn4 Gene Inhibits Nuclear Factor-κB (NF-κB) Protein Signaling/Inflammation and Reduces Remodeling after Myocardial Infarction

Wei²,

Wang

et al. 2012

Journal of Biological Chemistry

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Background:The causal role of calpain in myocardial remodeling after infarction has not been addressed. Results: Deficiency of Capn4 inhibited NF-B signaling and inflammation and reduced myocardial remodeling, dysfunction, and mortality after infarction. Conclusion: Calpain contributes to myocardial inflammation and remodeling after infarction. Significance: This study provides a significant insight into the function of calpain in post-myocardial infarction remodeling.

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“…Apoptosis-Apoptosis was determined by assessing caspase-3 activity and TUNEL staining positive cells as described previously (35).…”

Section: Real-time Reverse Transcription-polymerase Chain Reaction (Rmentioning

confidence: 99%

Deficiency of Capn4 Gene Inhibits Nuclear Factor-κB (NF-κB) Protein Signaling/Inflammation and Reduces Remodeling after Myocardial Infarction

Wei²,

Wang

et al. 2012

Journal of Biological Chemistry

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“…Deficiency of myocardial Rac1 or an inhibitor of Rac1 decreased NADPH oxidase activity and ROS generation in parallel with the improvement of postischemic function and myocardial infarction (44). Importantly, Rac1-induced activation of myocardial NADPH oxidase has been shown to increase mitochondrial ROS production and myocardial dysfunction (47,50). With increased myocardial Rac (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury

Talukder¹,

Elnakish

Yang³

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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. Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 304: H294 -H302, 2013. First published November 16, 2012 doi:10.1152/ajpheart.00367.2012.-The GTPbinding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O2 ·Ϫ ). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A novel transgenic mouse model with cardiac-specific overexpression of constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been reported with increased myocardial Rac-GTPase activity and O2 ·Ϫ generation. The goal of the present study was to determine signaling pathways related to increased myocardial ZmRacD and to what extent hearts with increased ZmRacD proteins are susceptible to I/R injury. The effect of myocardial I/R was examined in young adult wild-type (WT) and ZmRacD transgenic (TG) mice. In vitro reversible myocardial I/R for postischemic cardiac function and in vivo regional myocardial I/R for MI were performed. Following 20-min global ischemia and 45-min reperfusion, postischemic cardiac contractile function and heart rate were significantly reduced in TG hearts compared with WT hearts. Importantly, acute regional myocardial I/R (30-min ischemia and 24-h reperfusion) caused significantly larger MI in TG mice compared with WT mice. Western blot analysis of cardiac homogenates revealed that increased myocardial ZmRacD gene expression is associated with concomitant increased levels of NADPH oxidase subunit gp91 phox , O2 ·Ϫ , and P 21 -activated kinase. Thus these findings provide direct evidence that increased levels of active myocardial Rac renders the heart susceptible to increased postischemic contractile dysfunction and MI following acute I/R.

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“…Excessive blood homocysteine has been implicated in massive oxidative stress and decreased plasma total antioxidant capacity which could be reversed by both antioxidant and L-arginine supplementation [91,92]. Hyperhomocysteinemia, a common feature in diabetes mellitus, has been associated with increased cardiovascular disease risk and polyneuropathy in DM patients [93][94][95].…”

Section: Molecular Pathways Of Diabetes Mellitus Pathogenesismentioning

confidence: 99%

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

Ferrari¹

2017

Integr Obesity Diabetes

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Oxidative and nitrosative stress reactions are implicated in cell and organ damage due to diabetes mellitus. In both type 1 and type 2 DM there is a massive oxidative and nitrosative stresses which have been associated with intensive changes on both antioxidant enzyme systems (SOD, CAT, GPx, GSH) and total antioxidant capacity (TAC) causing peroxidative damage to lipids, proteins, nucleic acids and carbohydrates which can be used as DM biomarkers. Molecular pathophysiology of diabetes mellitus envolves induction of the the NFkB and p38-MAPK cell signaling pathways by Rac, TNF-α, TLR4, decrease of antioxidant defenses, and direct mitochondrial damage. Knowledge of molecular pathways is essential for research of newer preventive and therapeutic approaches in diabetes mellitus complications (atherosclerosis, myocardial damage, endothelial dysfunction, and renal failure).urine, feces, tissue sample), vegetable or fruit extract or even foods or pharmaceuticals [14][15][16].This article review and update the clinical, cellular, and molecular knowledge of free radicals and antioxidant defenses in diabetes mellitus. Ethiopathogenesis of diabetes mellitus I and IIDiabetes mellitus has been conceptualized as a group of metabolic disorders characterized by hyperglicemia as a result of insulin secretion failure and/or lacking of insulin action on target cells. The chronic diabetic hyperglicemic state has been related to long-term organ damage especially to the heart, endothelium and blood vessels, nerves, kidney, and eyes [17][18][19].

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Rac1 Is Required for Cardiomyocyte Apoptosis During Hyperglycemia

Cited by 172 publications

References 51 publications

Deficiency of Capn4 Gene Inhibits Nuclear Factor-κB (NF-κB) Protein Signaling/Inflammation and Reduces Remodeling after Myocardial Infarction

Deficiency of Capn4 Gene Inhibits Nuclear Factor-κB (NF-κB) Protein Signaling/Inflammation and Reduces Remodeling after Myocardial Infarction

Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

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